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Expression and Circulating Levels of Perlecan in Breast Cancer: Implications for Oestrogen Dependent Stromal Remodeling
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.ORCID iD: 0000-0003-2624-4671
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.ORCID iD: 0000-0001-5824-6263
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
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2020 (English)In: Journal of mammary gland biology and neoplasia, ISSN 1083-3021, E-ISSN 1573-7039, Vol. 25, p. 69-77Article in journal (Refereed) Published
Abstract [en]

Localised breast cancer can be cured by surgery and adjuvant treatments, but mortality remains high as some tumours metastasize early. Perlecan is a basement membrane (BM) protein involved in tumour development and progression. Here, mRNA and protein expression of perlecan, and mRNA expression of matrix degrading enzymes were studied in normal breast and invasive breast cancer, and correlated to prognostic risk factors, in particular oestrogen status. Moreover, plasma levels of perlecan were measured in patients with breast cancer and compared with controls. mRNA data was extracted from the Cancer Genome Atlas database. Perlecan protein expression was visualized using immunofluorescence and plasma levels measured by ELISA assay. Perlecan mRNA levels were twice as high in normal breast compared with breast cancer tissue. A strong correlation was found between mRNA expression of perlecan and several matrix-degrading enzymes in oestrogen receptor positive (ER+) tumours. Perlecan protein was localized to both epithelial and vascular BMs, but absent in the stroma in normal breast. In breast cancer, the expression of perlecan in epithelial BM was fragmented or completely lost, with a marked upregulation of perlecan expression in the stroma. Significantly higher levels of perlecan were found in plasma of ER+ patients when compared with ER- patients. This study shows that perlecan expression and degradation in breast cancer may be linked to the ER status of the tumour.

Place, publisher, year, edition, pages
2020. Vol. 25, p. 69-77
Keywords [en]
Perlecan, HSPG2, Breast cancer, Oestrogen receptor, extracellular matrix, Matrix metalloproteinases
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-169048DOI: 10.1007/s10911-020-09447-2ISI: 000517718100001PubMedID: 32124140OAI: oai:DiVA.org:umu-169048DiVA, id: diva2:1415730
Available from: 2020-03-19 Created: 2020-03-19 Last updated: 2020-03-19Bibliographically approved

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Jansson, MalinBilling, OlaHerdenberg, CarlLundin, ChristinaTolockiene, EgleNazemroaya, AnooshehSund, Malin

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