Chapter 5 │ Page 170 tumoral context. Transfection of Cx30 proteins into rat glioma cell lines, which have lost their Cx expression, reduced tumor cell growth and proliferation [85]. Likewise, transfection of Cx26 proteins into human hepatoma cells [86] and breast cancer cells [87] reduced their malignant potential, by inhibiting dedi erentiation, suppressing cell proliferation and tumor growth, and inducing apoptosis [86,87]. Mesnil et al. reported that out of several transfected Cx subtypes (e.g. Cx26, Cx40, Cx43), only the Cx26 proteins inhibited tumor growth and proliferation in HeLa cells, both in vitro and in vivo [88]. Moreover, di erent Cx species or combinations of them are expressed in di erent tumor types, suggesting that Cxs have cancer typespecific roles. For example, Cx43 proteins had no e ect on the proliferation of tumorigenic rat insulinoma cells [89], while they were able to reduce tumor growth and proliferation in human breast cancer tumors [90]. Taken together, these results suggest that Cxs can also act as tumor suppressors, dependent on Cx isotype, Cx expression levels, and cancer type. Interestingly, GJs in solid tumors are frequently decreased or missing in di erent cell populations within a tumor, suggesting that the loss of GJ coupling may be another characteristic of malignant transformation. Jamakosmanovic and Loewenstein observed that the electrical coupling found in normal thyroid cells was lost in thyroid cancer [91]. This phenomenon was also observed in cancerous and non-cancerous epithelial cells [92]. These results suggest that inhibition of intercellular communication through GJs in cancer cells likely a ects tissue growth and di erentiation. Restoration of GJs have therefore, resulted in a decrease in tumor progression. Daniel-Wójcik et al. demonstrated a direct link between Cx43GJ coupling intensity and cellular motility, a crucial aspect in cancer progression. An increase in Cx43 proteins at the cell-to-cell contact site and an enhancement of Cx43-GJs inhibited cancer cell motility in both prostate carcinoma and melanoma cells [93]. Another aspect to consider is that Cx-mediated tumor growth suppression can occur in a manner independent of GJ formation. Although Cx26,
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