umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Holmlund, Camilla
Publications (10 of 16) Show all publications
Faraz, M., Herdenberg, C., Holmlund, C., Henriksson, R. & Hedman, H. (2018). A protein interaction network centered on leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) regulates growth factor receptors. Journal of Biological Chemistry, 293(9), 3421-3435
Open this publication in new window or tab >>A protein interaction network centered on leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) regulates growth factor receptors
Show others...
2018 (English)In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 293, no 9, p. 3421-3435Article in journal (Refereed) Published
Abstract [en]

Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a tumor suppressor and a negative regulator of several receptor tyrosine kinases. The molecular mechanisms by which LRIG1 mediates its tumor suppressor effects and regulates receptor tyrosine kinases remain incompletely understood. Here, we performed a yeast two-hybrid screen to identify novel LRIG1-interacting proteins and mined data from the BioPlex (biophysical interactions of ORFeome-based complexes) protein interaction data repository. The putative LRIG1 interactors identified in the screen were functionally evaluated using a triple co-transfection system in which HEK293 cells were co-transfected with platelet-derived growth factor receptor α, LRIG1, and shRNAs against the identified LRIG1 interactors. The effects of the shRNAs on the ability of LRIG1 to down-regulate platelet-derived growth factor receptor α expression were evaluated. On the basis of these results, we present an LRIG1 protein interaction network with many newly identified components. The network contains the apparently functionally important LRIG1-interacting proteins RAB4A, PON2, GAL3ST1, ZBTB16, LRIG2, CNPY3, HLA-DRA, GML, CNPY4, LRRC40, and LRIG3, together with GLRX3, PTPRK, and other proteins. In silico analyses of The Cancer Genome Atlas data sets revealed consistent correlations between the expression of the transcripts encoding LRIG1 and its interactors ZBTB16 and PTPRK and inverse correlations between the transcripts encoding LRIG1 and GLRX3. We further studied the LRIG1 function–promoting paraoxonase PON2 and found that it co-localized with LRIG1 in LRIG1-transfected cells. The proposed LRIG1 protein interaction network will provide leads for future studies aiming to understand the molecular functions of LRIG1 and the regulation of growth factor signaling.

Place, publisher, year, edition, pages
The American Society for Biochemistry and Molecular Biology, 2018
Keywords
LRIG1, PDGFRA, PON2, PTPRK, ZBTB16, platelet-derived growth factor-C (PDGF-C), protein expression, protein-protein interaction, receptor tyrosine kinase, yeast two-hybrid
National Category
Basic Medicine
Identifiers
urn:nbn:se:umu:diva-147386 (URN)10.1074/jbc.M117.807487 (DOI)000426562800032 ()29317492 (PubMedID)
Available from: 2018-05-02 Created: 2018-05-02 Last updated: 2018-06-09Bibliographically approved
Karlsson, T., Kvarnbrink, S., Holmlund, C., Botling, J., Micke, P., Henriksson, R., . . . Hedman, H. (2018). LMO7 and LIMCH1 interact with LRIG proteins in lung cancer, with prognostic implications for early-stage disease. Lung Cancer, 125, 174-184
Open this publication in new window or tab >>LMO7 and LIMCH1 interact with LRIG proteins in lung cancer, with prognostic implications for early-stage disease
Show others...
2018 (English)In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 125, p. 174-184Article in journal (Refereed) Published
Abstract [en]

Objectives: The human leucine-rich repeats and immunoglobulin-like domains (LRIG) protein family comprises the integral membrane proteins LRIG1, LRIG2 and LRIG3. LRIG1 is frequently down-regulated in human cancer, and high levels of LRIG1 in tumor tissue are associated with favorable clinical outcomes in several tumor types including non-small cell lung cancer (NSCLC). Mechanistically, LRIG1 negatively regulates receptor tyrosine kinases and functions as a tumor suppressor. However, the details of the molecular mechanisms involved are poorly understood, and even less is known about the functions of LRIG2 and LRIG3. The aim of this study was to further elucidate the functions and molecular interactions of the LRIG proteins.

Materials and methods: A yeast two-hybrid screen was performed using a cytosolic LRIG3 peptide as bait. In transfected human cells, co-immunoprecipitation and co-localization experiments were performed. Proximity ligation assay was performed to investigate interactions between endogenously expressed proteins. Expression levels of LMO7 and LIMCH1 in normal and malignant lung tissue were investigated using qRT-PCR and through in silico analyses of public data sets. Finally, a clinical cohort comprising 355 surgically treated NSCLC cases was immunostained for LMO7.

Results: In the yeast two-hybrid screen, the two paralogous proteins LMO7 and LIMCH1 were identified as interaction partners to LRIG3. LMO7 and LIMCH1 co-localized and co-immunoprecipitated with both LRIG1 and LRIG3. Endogenously expressed LMO7 was in close proximity of both LRIG1 and LRIG3. LMO7 and LIMCH1 were highly expressed in normal lung tissue and down-regulated in malignant lung tissue. LMO7 immunoreactivity was shown to be a negative prognostic factor in LRIG1 positive tumors, predicting poor patient survival.

Conclusion: These findings suggest that LMO7 and LIMCH1 physically interact with LRIG proteins and that expression of LMO7 is of clinical importance in NSCLC.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Non-small cell lung cancer, Lung cancer, Prognosis, LRIG1, LRIG3, LMO7, LIMCH1
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-154070 (URN)10.1016/j.lungcan.2018.09.017 (DOI)000450378500025 ()30429017 (PubMedID)
Funder
Swedish Cancer SocietyThe Kempe FoundationsVästerbotten County Council
Available from: 2018-12-12 Created: 2018-12-12 Last updated: 2018-12-12Bibliographically approved
Mao, F., Holmlund, C., Faraz, M., Wang, W., Bergenheim, T., Kvarnbrink, S., . . . Hedman, H. (2018). Lrig1 is a haploinsufficient tumor suppressor gene in malignant glioma. Oncogenesis, 7, Article ID 13.
Open this publication in new window or tab >>Lrig1 is a haploinsufficient tumor suppressor gene in malignant glioma
Show others...
2018 (English)In: Oncogenesis, E-ISSN 2157-9024, Vol. 7, article id 13Article in journal (Refereed) Published
Abstract [en]

Recently, a genome-wide association study showed that a single nucleotide polymorphism (SNP) —rs11706832—in intron 2 of the human LRIG1 (Leucine-rich repeats and immunoglobulin-like domains 1) gene is associated with susceptibility to glioma. However, the mechanism by which rs11706832 affects glioma risk remains unknown; additionally, it is unknown whether the expression levels of LRIG1 are a relevant determinant of gliomagenesis. Here, we investigated the role of Lrig1 in platelet-derived growth factor (PDGF)-induced experimental glioma in mice by introducing mono-allelic and bi-allelic deletions of Lrig1 followed by inducing gliomagenesis via intracranial retroviral transduction of PDGFB in neural progenitor cells. Lrig1 was expressed in PDGFB-induced gliomas in wild-type mice as assessed using in situ hybridization. Intriguingly, Lrig1-heterozygous mice developed higher grade gliomas than did wild-type mice (grade IV vs. grade II/III, p = 0.002). Reciprocally, the ectopic expression of LRIG1 in the TB107 high-grade human glioma (glioblastoma, grade IV) cell line decreased the invasion of orthotopic tumors in immunocompromised mice in vivo and reduced cell migration in vitro. Concomitantly, the activity of the receptor tyrosine kinase MET was downregulated, which partially explained the reduction in cell migration. In summary, Lrig1 is a haploinsufficient suppressor of PDGFB-driven glioma, possibly in part via negative regulation of MET-driven cell migration and invasion. Thus, for the first time, changes in physiological Lrig1 expression have been linked to gliomagenesis, whereby the SNP rs11706832 may affect glioma risk by regulating LRIG1 expression.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-147385 (URN)10.1038/s41389-017-0012-8 (DOI)000429469500001 ()29391393 (PubMedID)
Available from: 2018-05-02 Created: 2018-05-02 Last updated: 2018-06-09Bibliographically approved
Karlsson, T., Kvarnbrink, S., Holmlund, C., Botling, J., Micke, P., Johansson, M., . . . Hedman, H. (2013). Interactions between LRIG proteins and LMO7 and the expression of LMO7 in human lung cancer.. Paper presented at 104th Annual Meeting of the American-Association-for-Cancer-Research (AACR), APR 06-10, 2013, Washington, DC. Cancer Research, 73(8: suppl 1), 5315
Open this publication in new window or tab >>Interactions between LRIG proteins and LMO7 and the expression of LMO7 in human lung cancer.
Show others...
2013 (English)In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 73, no 8: suppl 1, p. 5315-Article in journal (Refereed) Published
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-87195 (URN)10.1158/1538-7445.AM2013-5315 (DOI)000331220605337 ()
Conference
104th Annual Meeting of the American-Association-for-Cancer-Research (AACR), APR 06-10, 2013, Washington, DC
Available from: 2014-03-24 Created: 2014-03-24 Last updated: 2018-06-08Bibliographically approved
Rondahl, V., Holmlund, C., Karlsson, T., Wang, B., Faraz, M., Henriksson, R. & Hedman, H. (2013). Lrig2-deficient mice are protected against PDGFB-induced glioma. PLoS ONE, 8(9), e73635
Open this publication in new window or tab >>Lrig2-deficient mice are protected against PDGFB-induced glioma
Show others...
2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 9, p. e73635-Article in journal (Other academic) Published
Abstract [en]

Background: The leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins constitute an integral membrane protein family that has three members: LRIG1, LRIG2, and LRIG3. LRIG1 negatively regulates growth factor signaling, but little is known regarding the functions of LRIG2 and LRIG3. In oligodendroglial brain tumors, high expression of LRIG2 correlates with poor patient survival. Lrig1 and Lrig3 knockout mice are viable, but there have been no reports on Lrig2-deficient mice to date. Methodology/Principal Findings: Lrig2-deficient mice were generated by the ablation of Lrig2 exon 12 (Lrig2E12). The Lrig2E12-/- mice showed a transiently reduced growth rate and an increased spontaneous mortality rate; 20-25% of these mice died before 130 days of age, with the majority of the deaths occurring before 50 days. Ntv-a transgenic mice with different Lrig2 genotypes were transduced by intracranial injection with platelet-derived growth factor (PDGF) B-encoding replication-competent avian retrovirus (RCAS)-producing DF-1 cells. All injected Lrig2E12+/+ mice developed Lrig2 expressing oligodendroglial brain tumors of lower grade (82%) or glioblastoma-like tumors of higher grade (18%). Lrig2E12-/- mice, in contrast, only developed lower grade tumors (77%) or had no detectable tumors (23%). Lrig2E12-/- mouse embryonic fibroblasts (MEF) showed altered induction-kinetics of immediate-early genes Fos and Egr2 in response to PDGF-BB stimulation. However, Lrig2E12-/- MEFs showed no changes in Pdgfr alpha or Pdgfr beta levels or in levels of PDGF-BB-induced phosphorylation of Pdgfr alpha, Pdgfr beta, Akt, or extracellular signal-regulated protein kinases 1 and 2 (ERK1/2). Overexpression of LRIG1, but not of LRIG2, downregulated PDGFR alpha levels in HEK-293T cells. Conclusions: The phenotype of Lrig2E12-/- mice showed that Lrig2 was a promoter of PDGFB-induced glioma, and Lrig2 appeared to have important molecular and developmental functions that were distinct from those of Lrig1 and Lrig3.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-71044 (URN)10.1371/journal.pone.0073635 (DOI)000324515600112 ()
Note

Included in thesis in manuscript form

Available from: 2013-05-17 Created: 2013-05-17 Last updated: 2018-06-08Bibliographically approved
Asklund, T., Kvarnbrink, S., Holmlund, C., Wibom, C., Bergenheim, T., Henriksson, R. & Hedman, H. (2012). Synergistic Killing of Glioblastoma Stem-like Cells by Bortezomib and HADC Inhibitors.. Anticancer Research, 32(7), 2407-2413
Open this publication in new window or tab >>Synergistic Killing of Glioblastoma Stem-like Cells by Bortezomib and HADC Inhibitors.
Show others...
2012 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 7, p. 2407-2413Article in journal (Refereed) Published
Abstract [en]

Background: The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge. Materials and Methods: Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy. Results: Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments. Conclusion: These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.

Keywords
Glioblastoma, stem cells, proteasome inhibitor, HDAC inhibitor, TB101, R11 stem cells, U251 MG, GL 15 cells
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-56568 (URN)
Available from: 2012-06-25 Created: 2012-06-20 Last updated: 2019-11-25Bibliographically approved
Asklund, T., Kvarnbrink, S., Holmlund, C., Wibom, C., Bergenheim, T., Henriksson, R. & Hedman, H. (2012). Synergistic killing of Glioblastoma Stem-like cells by Bortezomib and HDAC Inhibitors. Anticancer Research, 32(7 ; Special Issue), 2407-2413
Open this publication in new window or tab >>Synergistic killing of Glioblastoma Stem-like cells by Bortezomib and HDAC Inhibitors
Show others...
2012 (English)In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 7 ; Special Issue, p. 2407-2413Article in journal (Refereed) Published
Abstract [en]

Background: The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge. Materials and Methods: Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy. Results: Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments. Conclusion: These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.

Place, publisher, year, edition, pages
International Institute of Anticancer Research, 2012
Keywords
Glioblastoma, stem cells, proteasome inhibitor, HDAC inhibitor, TB101, R11 stem cells, U251 MG, GL15 cells
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-57605 (URN)000306254300003 ()
Available from: 2012-08-08 Created: 2012-08-08 Last updated: 2018-06-08Bibliographically approved
Yi, W., Holmlund, C., Nilsson, J., Inui, S., Lei, T., Itami, S., . . . Hedman, H. (2011). Paracrine regulation of growth factor signaling by shed leucine-rich repeats and immunoglobulin-like domains 1. Experimental Cell Research, 317(4), 504-512
Open this publication in new window or tab >>Paracrine regulation of growth factor signaling by shed leucine-rich repeats and immunoglobulin-like domains 1
Show others...
2011 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 317, no 4, p. 504-512Article in journal (Refereed) Published
Abstract [en]

Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a recently discovered negative regulator of growth factor signaling. The LRIG1 integral membrane protein has been demonstrated to regulate various oncogenic receptor tyrosine kinases, including epidermal growth factor (EGF) receptor (EGFR), by cell-autonomous mechanisms. Here, we investigated whether LRIG1 ectodomains were shed, and if LRIG1 could regulate cell proliferation and EGF signaling in a paracrine manner. Cells constitutively shed LRIG1 ectodomains in vitro, and shedding was modulated by known regulators of metalloproteases, including the ADAM17 specific inhibitor TAPI-2. Furthermore, shedding was enhanced by ectopic expression of Adam17. LRIG1 ectodomains appeared to be shed in vivo, as well, as demonstrated by immunoblotting of mouse and human tissue lysates. Ectopic expression of LRIG1 in lymphocytes suppressed EGF signaling in co-cultured fibroblastoid cells, demonstrating that shed LRIG1 ectodomains can function in a paracrine fashion. Purified LRIG1 ectodomains suppressed EGF signaling without any apparent downregulation of EGFR levels. Taken together, the results show that the LRIG1 ectodomain can be proteolytically shed and can function as a non-cell-autonomous regulator of growth factor signaling. Thus, LRIG1 or its ectodomain could have therapeutic potential in the treatment of growth factor receptor-dependent cancers.

Place, publisher, year, edition, pages
New York: Academic Press, 2011
Keywords
LRIG1, shedding, EGFR, cell proliferation, TACE, ADAM17
National Category
Cell Biology Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-39290 (URN)10.1016/j.yexcr.2010.11.005 (DOI)21087604 (PubMedID)
Available from: 2011-01-20 Created: 2011-01-20 Last updated: 2018-06-08Bibliographically approved
Holmlund, C. (2010). Identification and investigations of leucine-rich repeats and immunoglobulin-like domains protein 2 (LRIG2). (Doctoral dissertation). Umeå: University
Open this publication in new window or tab >>Identification and investigations of leucine-rich repeats and immunoglobulin-like domains protein 2 (LRIG2)
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Receptor tyrosine kinases (RTKs) constitute a family of proteins controlling cell growth and proliferation and whose activities are tightly controlled in normal cells. LRIG1 is a negative regulator of RTK signaling and is a proposed tumor suppressor. The aim of this thesis was to identify and study possible paralogs of LRIG1. By using the basic local alignment search tool and cDNA cloning, a human mRNA sequence with similarity to LRIG1 was identified and named LRIG2. By fluorescence in situ hybridization analysis, LRIG2 was found to reside on chromosome 1p13. The LRIG2 amino acid sequence was 47% identical to LRIG1, and the predicted protein domain organization was the same as that of LRIG1. Antibodies against LRIG2 were developed and the apparent molecular weight of the protein was determined to be 132 kDa by SDS-polyacrylamide gel electrophoresis and Western blot analysis. The sub-cellular localization was studied by cell surface biotinylation experiments and confocal fluorescence laser microscopy, which revealed that LRIG2 resided at the cell surface and in the cytoplasm.

The expression patterns of LRIG2 mRNA, during development and in adult tissues, were evaluated using whole-mount in situ hybridization and quantitative real-time RT-PCR, respectively. In E10.5, E11.5 and E12.5 mouse embryos, the Lrig2 expression domains were both overlapping and unique as compared to the expression domains of Lrig1 and the third family member, Lrig3. In adult human tissues, the most prominent LRIG2 mRNA expression was found in skin, uterus and ovary. To study the developmental and physiological role of LRIG2, Lrig2 knock-out mice were generated. The knock-out mice were born at Mendelian frequencies without any apparent morphological abnormalities. However, Lrig2 knock-out mice showed reduced body weight between 5 days and 12-15 weeks of age, increased mortality, and impaired reproductive capacity.

To study the role of LRIG2 as a prognostic factor in oligodendroglioma, LRIG2 expression was analyzed in 65 human oligodendrogliomas by immunohistochemistry. Cytoplasmic LRIG2 expression was an independent prognostic factor associated with poor oligodendroglioma patient survival. The possible functional role of LRIG2 in oligodendroglioma biology was further investigated using the RCAS/tv-a mouse model. Tumors resembling human oligodendroglioma were induced by intracranial injection of PDGFB carrying RCAS retroviruses into newborn Ntv-a mice. Lrig2 wild-type animals developed tumors at a higher frequency and of higher malignancy than the Lrig2 knock-out mice. This result supports the notion that LRIG2 promotes PDGF-induced oligodendroglioma genesis. A possible molecular mechanism was revealed as LRIG2 overexpression increased PDGFRa levels in transfected cells. In summary, we identified a new gene named LRIG2, showed that it is expressed in a variety of tissues during development and in adulthood, knocked it out and found that it was required for proper animal growth, health, and reproduction. We also found that Lrig2 expression promoted PDGF-induced oligodendroglioma genesis and was associated with poor oligodendroglioma patient survival, possibly via a PDGFRa stabilizing function.

Place, publisher, year, edition, pages
Umeå: University, 2010. p. 52
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1346
Keywords
LRIG, PDGF, oligodendroglioma
National Category
Medical and Health Sciences
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-33784 (URN)978-91-7459-011-1 (ISBN)
Public defence
2010-05-28, Sal 244 Lionssalen, By 7, Norrlands universitetssjukhus, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2010-05-10 Created: 2010-05-06 Last updated: 2018-06-08Bibliographically approved
Holmlund, C., Haapasalo, H., Yi, W., Raheem, O., Brännström, T., Bragge, H., . . . Hedman, H. (2009). Cytoplasmic LRIG2 expression is associated with poor oligodendroglioma patient survival.. Neuropathology (Kyoto. 1993), 29(3), 242-247
Open this publication in new window or tab >>Cytoplasmic LRIG2 expression is associated with poor oligodendroglioma patient survival.
Show others...
2009 (English)In: Neuropathology (Kyoto. 1993), ISSN 0919-6544, E-ISSN 1440-1789, Vol. 29, no 3, p. 242-247Article in journal (Refereed) Published
Abstract [en]

The three leucine-rich repeats and immunoglobulin-like domains (LRIG) genes encode integral membrane proteins. Of these, LRIG1 negatively regulates growth factor signaling and is implicated as a tumor suppressor in certain malignancies. In astrocytic tumors, the subcellular distribution of LRIG proteins is associated with specific clinicopathological features and patient survival. The role of LRIG proteins in oligodendroglioma has not previously been studied. Here we used immunohistochemistry to analyze the expression of the LRIG proteins in 63 oligodendroglial tumors, and evaluated possible associations between LRIG protein expression and clinicopathological parameters. Notably, cytoplasmic LRIG2 expression was found to be an independent prognostic factor associated with poor oligodendroglioma patient survival. This is the first report of an LRIG protein showing a negative effect on survival, suggesting that LRIG2 might have a function different from that of LRIG1, and possibly contributing to the etiology of oligodendroglioma.

Keywords
immunohistochemistry, LRIG proteins, LRIG2, oligodendroglioma, patient survival
National Category
Cancer and Oncology
Research subject
Oncology
Identifiers
urn:nbn:se:umu:diva-11524 (URN)10.1111/j.1440-1789.2008.00970.x (DOI)18992012 (PubMedID)
Available from: 2009-01-13 Created: 2009-01-13 Last updated: 2018-06-09Bibliographically approved
Organisations

Search in DiVA

Show all publications