Calbindin Expression And The Metastatic Phenotype

The ability of steroids to influence the expression of calbindins has led to investigations aimed at examining their potential involvement in the development and growth of tumours, their progression, and prognosis. Watanabe et al. (1994) investigated CBD levels of lung cancers. The levels of CBD were low in normal lung tissue, but its expression was higher in lung cancers, with SCLC tissue expressing greater amounts than non-SCLC (NSCLC). Furthermore, CBD levels correlated with progression of NSCLC to advanced stages of the disease involving metastatic involvement of the lymph nodes. Upon investigating cell lines derived from these tumours, Watanabe et al. (1994) noticed that CBD expression might also relate to the expression of neuroendocrine-related paraneoplastic properties of these tumours. They found that the CBD could be used to differentiate classical SCLC from variant

SCLC. The specificity and sensitivity with which this could be achieved was comparable to the neuroendocrine marker neurone-specific enolase.

Significant differences also have been noted in the expression of CBD in human colonic cell lines derived from primary tumours and those derived from metastatic tumours. Sampson-Johannes et al. (1996) found that SW480 cells obtained from primary colorectal tumours did not express CBD, but in sharp contrast, SW620 cells derived from metastatic tumours did. They also demonstrated that SW480 cells were not capable of colonising human foetal lung tissue transplanted into SCID-hu mice, but SW620 cells colonised the grafts upon intravenous introduction into the animals. Furthermore, SW620 cells expressed sialyl Lewis-x and Lewis-a antigens which are conducive to metastatic spread at far higher levels than SW480, which were unable to colonise the foetal lung grafts. On the basis of these results, the authors suggest that the appearance of the metastatic ability could be associated with the acquisition of CBD expression. It ought to be recognised, however, that this experimental model is too remote from the spontaneous metastasis. The differences in the abilities of the two cell types to localise in foetal lung grafts may simply reflect their adhesive capabilities, rather than CBD expression. Some preliminary work has been reported (Castro et al. 1998) that relates the value of CBD expression to prognosis of lung cancer.

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