Epidermal growth factor receptor modulates the tumorigenic potential of melanoma

Abstract

Potential contribution of the Epidermal Growth Factor Receptor (EGFR) in melanoma immunobiology remains unclear, in part due to a lack of experimental models. We demonstrated previously that B16F10 melanoma transfected with the full length cDNA of the human EGFR increases the tumor cell proliferation in vitro. To further study its contribution in vivo, EGFR-transfected B16F10 cells were inoculated in syngenic C57BL/6 mice and its tumorigenic capacity was compared with the parental melanoma. Contrary to the observed in vitro effect, EGFR-transfected B16F10 cells displayed a delayed tumor growth rate in vivo, correlating inversely to the transgene expression. Interestingly, resulting tumors showed a downregulation of the EGFR transgene expression. Contrastingly, parental and EGFR-transfected B16F10 cells exhibited a similar tumorigenic potential in immunocompromised subjects, persisting the EGFR transgene expression. These results document the adaptability of melanoma to growth in immunocompetent individuals. Moreover, the potential EGFR expression during the melanoma outgrowth that would be downregulated by interacting with the host immune system during the tumor evolution is not excluded and which may be dissected in this model.

Melanoma: from mutations to medicine

“…Together with the paucity of driver EGFR mutations in melanoma, such results have dampened preclinical enthusiasm for EGFR as a target in this malignancy. In fact, one recent study found that EGFR expression may modestly suppress melanoma growth in a B16 model (Diaz et al 2009). …”

Stromal Microenvironment Alterations in Malignant Melanoma

“…This is in contrast to in vivo studies using implantation of melanoma cells, where decreased EGFR together with growth inhibition have been documented. It seems that EGFR levels are modulated during melanoma growth, with one of important modulators being the immune system (Diaz et al, 2009). EGFR is increased not only in melanoma lesions including both early-and late-stage melanomas but also in benign nevi.…”