Proteomics-aided search for extracellular matrix signatures of colorectal hepatic metastases ex vivo

Thesis

Hepatic metastases are one of the most dangerous consequences of colorectal cancer, and their occurrence often results in poor prognosis and death. There is a need to improve survival and quality of life for patients with colorectal liver metastases.

In this work, we utilised mass-spectrometry method to identify proteins characteristic of mouse colorectal liver metastasis matrisome and further confirmed the expression of some of them in liver metastasis by immunohistochemistry.

We showed ex vivo that S100-A11 and annexin A1 are significantly overexpressed in hepatic metastases according to two different mass-spectrometry approaches. Further, we demonstrated that both S100-A11 and annexin A1 are expressed by cancer cell lines MC38, Pan02, HCT116, HT29, and LoVo in culture. Also, using human xenografts in mice, we were able to identify the source of these proteins by mass-spectrometry. Obtained immunohistochemistry images suggest that S100-A11 and annexin A1 may for a complex within the tumour, which is in agreement with literature data. We next confirmed by immunohistochemistry that annexin A1 is markedly overexpressed in colorectal hepatic metastases, as well as in human liver metastases, as compared to adjacent healthy tissue. Finally, we found that CD45⁺ but not Ly6G⁺ or CD11b⁺ cells express annexin A1 in colorectal hepatic metastases.

Our findings indicate that S100-A11 and annexin A1 may play a role in colorectal liver metastases development. Further in-depth research is necessary to elucidate their impact on tumour biology.

Authors: Yuzhalin, A

• Publication date: 2014
• Type of award: MSc by Research
• Level of award: Masters
• Awarding institution: Oxford University, UK
• Language: English
• Keywords: cancer; matrisome; proteomics; extracellular matrix
• Subjects: Protein chemistry; Biochemistry; Oncology; Mass spectrometry; Tumours