Summary It has been suggested that the selective loss of E-cadherin expression can generate invasiveness in human carcinoma cells and might be a predictor of metastasis. Frozen sections of samples from 44 patients, 43 with suspected large bowel cancer and one with a liver recurrence were examined for E-cadherin expression using the antibody 6F9 specific for the human E-cadherin molecule. Twelve of the 40 patients with carcinoma already had lymph node involvement at the time of surgery. Samples from the primary carcinomas of only nine of these 12 patients showed reduced E-cadherin expression. However, the one lymph node with metastatic spread examined did show reduced E-cadherin expression. Four of the 40 carcinoma patients had liver involvement at the time of surgery. The primary carcinoma samples from only three of these four patients showed reduced E-cadherin expression. In addition only two out of the three liver metastases examined showed reduced expression. The primary carcinoma samples from seven patients with no evidence of tumour spread also exhibited reduced expression. Overall, analysis of the data suggests that there is no absolute correlation between reduced E-cadherin expression and tumour spread in carcinomas of the large bowel. E-cadherin (also known as Arc-1, uvomorulin and cell CAM 120/80) is one of a group of functionally related, integral membrane glycoproteins responsible for calcium-dependent cell-cell adhesion. Cadherins are responsible for the movement and rearrangement of cell collectives during embryogenesisi (Takeichi, 1988) and for the orderly structure of differentiated tissue. Cell transfection studies with E-cadherin cDNA in rodent systems have demonstrated directly that cadherin molecules are involved in cell-cell binding (Nagafuchi et al., 1987;Mege et al., 1988). Moreover, Behrens et al. (1989) demonstrated that epithelial cells deprived of their E-cadherin function by the addition of anti-E-cadherin antibodies, not only became less adhesive but became able to invade collagen gels and embryonal heart tissue. Shimoyama and co-workers (1989) also reported that colonies of cultured epithelial cells became dissociated and mobile after the addition of anti-E-cadherin antibody.Expression of E-cadherin has been studied in tissue sections from a variety of well and poorly differentiated human tumours, but not those arising in the large bowel, using immunohistochemical and immunofluorescence techniques (Eidelman et al., 1989;Shimoyama et al., 1989;Pfisterer et al., 1990; Shimoyama & Hirohashi, 1991a,b;Schipper et al., 1991). For the most part, E-cadherin expression has been shown to correlate with differentiation status, with lower levels of expression being observed in poorly differentiated tumours. This correlation with differentiation status has been observed for ovarian carcinomas (Pfisterer et al., 1990) and squamous carcinomas of the head and neck (Schipper et al., 1991 (Hashimoto et al., 1989) and the absence of expression in a grade IV hepatocellular carcinoma that went on to ...

A reduction in cell adhesiveness and cell invasion are essential steps in tumour progression to metastasis. In the present study two out of seven colorectal carcinoma cell lines exhibited reduced expression of the cell-cell adhesion molecule E-cadherin as assessed by immunofluorescence. The same two cell lines were invasive in the collagen gel and membrane invasion culture system invasion assays. Addition of anti-E-cadherin antibody to a non-invasive carcinoma cell line caused the cells to assume a dissociated morphology on plastic and to become invasive in collagen gels. This demonstrates a causal role for E-cadherin in the maintenance of intercellular adhesion and the suppression of tumour cell invasion and possibly metastasis in colorectal tumour cells.