Aberrant expression of vimentin predisposes oral premalignant lesion derived cells towards transformation

We have previously reported the aberrant expression of vimentin in human oral premalignant lesions and a 4-Nitroquinoline 1-oxide (4NQO) model of rat lingual carcinogenesis. Hence, we wanted to understand whether the expression of vimentin in early stage contributes to the process of transformation.

Vimentin was stably expressed in oral premalignant lesion derived cells (vimentin negative) and various transformation related phenotypic assays were performed. Since vimentin alone failed to transform the cells, an additional carcinogenic stimulus benzo[a]pyrene (BP) was used. Concomitantly, immunohistochemistry (IHC) was performed on oral leukoplakia and tumor tissues for studying the expression of vimentin and E-cadherin.

Exogenous expression of vimentin led to the appearance of EMT and stemness-related signatures. Further, upon BP treatment, vimentin expressing clones showed an increase in vitro and in vivo transformation efficiency. Importantly, high vimentin-low E-cadherin expression significantly correlated with the grade of dysplasia, as also with the lymph node metastasis in oral tumors.

Our study suggests that the expression of vimentin in early stages may be beneficial, although not sufficient to achieve transformation. Further, high vimentin-low E-cadherin expression, if validated in more number of early oral lesions, may prove useful in the identification of high risk human premalignant lesions.