Proteomics analysis of the matrisome from MC38 experimental mouse liver metastases.
Yuzhalin AE., Lim SY., Gordon-Weeks AN., Fischer R., Kessler BM., Yu D., Muschel RJ.
Background and Aim: 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 weight 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 extracellular matrix from MC38 mouse liver metastases using our optimized method of mild detergent solubilization followed by biochemical enrichment. Methods: The matrices were subjected to label-free quantitative mass spectrometry analysis, revealing proteins highly abundant in the metastatic matrisome. Results: The resulting list of differentially expressed proteins significantly predicted survival in patients with colorectal cancer but not other cancers with strong involvement of the extracellular matrix 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 to cancer cells of other origin, and also overrepresented in human primary colorectal lesions as well as hepatic metastases in comparison with their adjacent healthy tissue counterparts. Conclusions: 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.