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2022 (English)In: Cancers, ISSN 2072-6694, Vol. 14, no 14, article id 3396Article in journal (Refereed) Published
Abstract [en]
Circulating type IV collagen (cCOL IV) is a potential biomarker for patients with colorectal liver metastases (CLM) who present with elevated levels of COL IV in both CLM tissue and circulation. This study aimed to establish the cellular origin of elevated levels of COL IV and analyze circulating COL IV in CLM patients. The cellular source was established through in situ hybridization, immunohistochemical staining, and morphological evaluation. Cellular expression in vitro was assessed by immunofluorescence. Tissue expression of COL IV-degrading matrix metalloproteinases (MMPs)-2, -7, -9, and -13 was studied with immunohistochemical staining. Plasma levels of COL IV in CLM patients and healthy controls were analyzed with ELISA. This study shows that cancer-associated fibroblasts (CAFs) express COL IV in the stroma of CLM and that COL IV is expressed in vitro by fibroblasts but not by tumor cells. MMP-2, -7, -9, and -13 are expressed in CLM tissue, mainly by hepatocytes and immune cells, and circulating COL IV is significantly elevated in CLM patients compared with healthy controls. Our study shows that stromal cells, not tumor cells, produce COL IV in CLM, and that circulating COL IV is elevated in patients with CLM.
Place, publisher, year, edition, pages
MDPI, 2022
Keywords
CAF, circulating biomarkers, COL IV, colorectal cancer, fibroblasts, liver metastases, MMP, tumor stroma, type IV collagen
National Category
Surgery
Identifiers
urn:nbn:se:umu:diva-199091 (URN)10.3390/cancers14143396 (DOI)000833244000001 ()35884455 (PubMedID)2-s2.0-85136451220 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationVästerbotten County CouncilSwedish Cancer SocietyCancerforskningsfonden i NorrlandThe Kempe FoundationsUmeå University
2022-10-052022-10-052025-04-16Bibliographically approved