Type IV collagen is a tumour stroma-derived biomarker for pancreas cancer.
BACKGROUND
Pancreas cancer is a dreaded disease with high mortality, despite progress in surgical and oncological treatments in recent years. The field is hampered by a lack of good prognostic and predictive tumour biomarkers to be used during follow-up of patients.


METHODS
The circulating level of type IV collagen was measured by ELISA in pancreas cancer patients and controls. The expression pattern of type IV collagen in normal pancreas, pancreas cancer tissue and in pancreas cancer cell lines was studied by immunofluorescence and Western blot techniques.


RESULTS
Patients with pancreas cancer have significantly increased circulating levels of type IV collagen. In pancreas cancer tissue high levels of type IV collagen expression was found in close proximity to cancer cells in the tumour stroma. Furthermore, pancreas cancer cells were found to produce and secrete type IV collagen in vitro, which in part can explain the high type IV collagen expression observed in pancreas cancer tissue, and the increased circulating levels in pancreas cancer patients. Of clinical importance, our results show that the circulating level of type IV collagen after surgery is strongly related to prognosis in patients treated for pancreas cancer by pancreatico-duodenectomy with curative intent. Persisting high levels of circulating type IV collagen after surgery indicates a quick relapse in disease and poor survival.


CONCLUSIONS
Our results most importantly show that stroma related substances can be evaluated as potential cancer biomarkers, and thereby underline the importance of the tumour microenvironment also in this context.
Ohlund
D
D
Department of Surgical and Perioperative Sciences, Surgery, Umeå University, Umeå, Sweden.
Lundin
C
C
Ardnor
B
B
Oman
M
M
Naredi
P
P
Sund
M
M
D000230:Adenocarcinoma / Q000097:blood* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000097:blood*; D015153:Blotting, Western; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D024141:Collagen Type IV / Q000096:biosynthesis / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000097:blood* / Q000473:pathology / Q000601:surgery; D017154:Stromal Cells / Q000473:pathology
D014408:Biomarkers, Tumor; D024141:Collagen Type IV