Publication date: Mar 26, 2019
The tumor microenvironment has been compared to a non-healing wound involving a complex interaction between multiple cell types. Schwann cells, the key regulators of peripheral nerve repair, have recently been shown to directly affect non-neural wound healing. Their role in cancer progression, however, has been largely limited to neuropathic pain and perineural invasion. In this study, we showed that melanoma activated otherwise dormant functions of Schwann cells aimed at nerve regeneration and wound healing. Such reprogramming of Schwann cells into repair-like cells occurred during the destruction and displacement of neurons as the tumor expanded and via direct signaling from melanoma cells to Schwann cells, resulting in activation of the nerve injury response. Melanoma-activated Schwann cells significantly altered the microenvironment through their modulation of the immune system and the extracellular matrix in a way that promoted melanoma growth in vitro and in vivo. Local inhibition of Schwann cell activity following cutaneous sensory nerve transection in melanoma orthotopic models significantly decreased the rate of tumor growth. Tumor-associated Schwann cells, therefore, can have a significant pro-tumorigenic effect and may present a novel target for cancer therapy.
Shurin, G.V., Kruglov, O., Ding, F., Lin, Y., Hao, X., Keskinov, A.A., You, Z., Lokshin, A.E., LaFramboise, W.A., Falo, L.D., Shurin, and Bunimovich, Y.L. Melanoma-induced reprogramming of Schwann cell signaling aids tumor growth. 22090. 2019 Cancer Res.
- Low-level laser irradiation potentiates anticancer activity of p-coumaric acid against human malignant melanoma cells.