Several growth factors are involved in the control of human colorectal cancer cell proliferation by autocrine, paracrine, and juxtacrine mechanisms. A major family of colon tumour growth regulators is represented by the epidermal growth factor (EGF)-related growth factors such as EGF transforming growth factor α (TGF-α), amphiregulin (AR), and CRIPTO. All these peptides, with the exception of CRIPTO, bind to and activate the EGF receptor. TGF-α, AR and CRIPTO are coexpressed in the majority of human colorectal cancer cell lines and primary and metastatic colorectal cancers. In general the frequency and the level of expression of these proteins are higher in malignant cells as compared to benign lesions and to normal colon epithelium. Interestingly, only 2 to 5% of normal colonic mucosa express detect able levels of CRIPTO mRNA and protein, whereas high levels of CRIPTO expression are found in approximately 50% of adenomas and in 70 to 85% of primary and metastatic cancers. Furthermore, inhibition of TGF-α, AR or CRIPTO production by a specific antisense approach determines in vitro and, in certain cases, in vivo growth inhibition of human colon cancer cells. These data suggest that TGF-α, AR and CRIPTO can function as colorectal autocrine tumour growth factors and that the differential expression of CRIPTO may be used as a tumour marker for human colorectal cancer.
|Number of pages||11|
|Journal||FORUM - Trends in Experimental and Clinical Medicine|
|Publication status||Published - 1995|
- Colorectal cancer
- Epidermal growth factor receptor
- Transforming growth factor α
ASJC Scopus subject areas