Liver Cancer, Males Vs. Females, And ZebraFish

At left, adult female zebrafish. By Azul (Own work) [Copyrighted free use], via Wikimedia Commons

Liver cancer is more prevalent in men. There may be both biological and lifestyle reasons for this. To study possible biological mechanism, a zebrafish model was used. Abstract:

Hepatocellular carcinoma (HCC) is more prevalent in men than women, but the reason for this gender disparity is not well understood. To investigate whether zebrafish could be used to study the gender disparity of HCC, we compared the difference of liver tumorigenesis between female and male fish during early tumorigenesis and long-term tumor progression in our previously established inducible and reversible HCC model - the krasV12 transgenic zebrafish. We found that male fish developed HCC faster than females. The male tumors were more severe from the initiation stage, characteristic of higher proliferation, activation of WNT/β-catenin pathway and loss of cell adhesion. During long-term tumor progression, the male tumors developed into more advanced multi-nodular tumors, whereas the female tumors remain uniform and homogenous. Moreover, regression of male tumors required longer time. We further investigated the role of sex hormones in krasV12 transgenic fish. Estrogen treatment showed tumor suppressing effect during early tumorigenesis through inhibiting cell proliferation, whereas androgen accelerated tumor growth by promoting cell proliferation. Overall, our study presented the zebrafish as a useful animal model for study of gender disparity of HCC.

Obviously, humans are not zebrafish and it is not certain that the possible hormonal mechanism identified in the fish applies to humans, but it is a possible avenue for study.