Dissemination of primary
tumors to distant anatomical sites has a substantial negative impact on patient prognosis. The liver is a common site for
metastases from
colorectal cancer, and patients with hepatic
metastases have generally much shorter survival, raising a need to develop and implement novel strategies for targeting metastatic disease. The extracellular matrix (ECM) is a meshwork of highly crosslinked, insoluble high-molecular-mass
proteins maintaining tissue integrity and establishing cell-cell interactions. Emerging evidence identifies the importance of the ECM in
cancer cell migration, invasion, intravasation, and
metastasis. Here, we isolated the ECM from MC38 mouse liver
metastases using our optimized method of mild
detergent solubilization followed by biochemical enrichment. The matrices were subjected to label-free quantitative mass spectrometry analysis, revealing
proteins highly abundant in the metastatic matrisome. The resulting list of
proteins upregulated in the ECM significantly predicted survival in patients with
colorectal cancer but not other
cancers with strong involvement of the ECM component. One of the
proteins upregulated in liver metastatic ECM,
annexin A1, was not previously studied in the context of
cancer-associated matrisome. Here, we show that
annexin A1 was markedly upregulated in
colon cancer cell lines compared with
cancer cells of other origin and also over-represented in human primary colorectal lesions, as well as hepatic
metastases, compared with their adjacent healthy tissue counterparts. In conclusion, our study provides a comprehensive ECM characterization of MC38 experimental liver
metastases and proposes
annexin A1 as a putative target for this disease.NEW & NOTEWORTHY Here, the authors provide an extensive proteomics characterization of murine
colorectal cancer liver
metastasis matrisome (the ensemble of all extracellular matrix molecules). The findings presented in this study may enable identification of therapeutic targets or
biomarkers of hepatic
metastases.