Up-regulation of collagen proteins in colorectal liver metastasis compared with normal liver tissue

Abstract

Edited by Xiao-Fan WangChanges to extracellular matrix (ECM) structures are linked to tumor cell proliferation and metastasis. We previously reported that naturally occurring peptides of collagen type I are elevated in urine of patients with colorectal liver metastasis (CRLM). In the present study, we took an MS-based proteomic approach to identify specific collagen types that are up-regulated in CRLM tissues compared with healthy, adjacent liver tissues from the same patients. We found that 19 of 22 collagen-␣ chains are significantly up-regulated (p < 0.05) in CRLM tissues compared with the healthy tissues. At least four collagen-␣ chains were absent or had low expression in healthy colon and adjacent tissues, but were highly abundant in both colorectal cancer (CRC) and CRLM tissues. This expression pattern was also observed for six noncollagen colon-specific proteins, two of which (CDH17 and PPP1R1B/DARP-32) had not previously been linked to CRLM. Furthermore, we observed CRLM-associated up-regulation of 16 proteins (of 20 associated proteins identified) known to be required for collagen synthesis, indicating increased collagen production in CRLM. Immunohistochemistry validated that collagen type XII is significantly upregulated in CRLM. The results of this study indicate that most collagen isoforms are up-regulated in CRLM compared with healthy tissues, most likely as a result of an increased collagen production in the metastatic cells. Our findings provide further insight into morphological changes in the ECM in CRLM and help explain the finding of tumor metastasis-associated proteins and peptides in urine, suggesting their utility as metastasis biomarkers. 2 The abbreviations used are: ECM, extracellular matrix; CRC, colorectal cancer; CRLM, colorectal liver metastasis; IQR, interquartile range; FIB, liver fibrosis; IHC, immunohistochemistry; PEPD, Xaa-Pro dipeptidase; Hyp, hydroxyproline; iBAQ, intensity-based absolute quantification.

Collagen analysis with mass spectrometry

“…In breast cancer, Ma et al () have shown upregulation of the gene expression of 23 collagen genes and that of 94 other ECM genes. Furthermore, Naba et al () and van Huizen et al () have shown that the collagen composition of colorectal liver metastasis is significantly different from that of healthy liver tissue.…”

“…A change in collagen turnover caused by external influences (eg, scurvy or fibrosis) also results in a diseased state. Collagen also plays a role in tumor development and metastasis (Fang et al, ; Xiong & Xu, ; van Huizen et al, ). For the reader interested in the role of collagen in fibrosis we recommend the review of Karsdal et al ().…”

Differential clinical significance of COL5A1 and COL5A2 in tongue squamous cell carcinoma

“…There are three major isoforms of COL5, formed by the combination of three different polypeptide alpha chains (A1, A2, and A3), the collagen type V alpha 1 (COL5A1) homotrimer, the COL5A1/collagen type V alpha 2 (COL5A2)/collagen type V alpha 3 (COL5A3) heterotrimer, and the (COL5A1) 2 /COL5A2 heterotrimer which is the most functional . It was reported that certain polypeptide chains of certain type of collagen are highly abundant in certain cancer . Moreover, abnormal COL5 expression can promote tumor malignancy and progression in various types of cancer.…”

“…3 It was reported that certain polypeptide chains of certain type of collagen are highly abundant in certain cancer. 4 Moreover, abnormal COL5 expression can promote tumor malignancy and progression in various types of cancer. However, its clinical role in TSCC is still not well understood.…”

Proteômica de biopsias líquidas (sérica e urina) como biomarcadores nos adenocarcinomas colorretais

“…O colágeno tipo 1 é o mais abundante dentre os da família do colágeno, sendo formado por duas cadeias, alfa-1 (COL1A1) e alfa-2 (COL1A2)[90,91].A exata função desta proteína ainda não foi bem elucidada, porém apesar de grande parte dos estudos apontarem que proteínas colágeno estão hiper-regulada no CCR, podendo ser apontada por alguns como preditora de metástases hepática, o COL1A2 aparenta apresentar regulação negativa no CCR devido a hipermetilação do seu gene codificador. Um estudo realizado in vitro constatou que o COL1A2 inibe a progressão da neoplasia[57,[90][91][92].…”