The Role of Melanoma Cell-Stroma Interaction in Cell Motility, Invasion, and Metastasis

Frontiers in Medicine

Nikolas K. Haass¹  Robert J. Ju²  Samantha J. Stehbens² 

[1] Discipline of Dermatology, University of Sydney, Sydney, NSW, Australia;The University of Queensland, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, Australia;

关键词: melanoma;    motility;    invasion;    metastasis;    microenviroment;    cytokines;   

DOI  :  10.3389/fmed.2018.00307

来源: DOAJ

【 摘 要 】

The importance of studying cancer cell invasion is highlighted by the fact that 90% of all cancer-related mortalities are due to metastatic disease. Melanoma metastasis is driven fundamentally by aberrant cell motility within three-dimensional or confined environments. Within this realm of cell motility, cytokines, growth factors, and their receptors are crucial for engaging signaling pathways, which both mediate crosstalk between cancer, stromal, and immune cells in addition to interactions with the surrounding microenvironment. Recently, the study of the mechanical biology of tumor cells, stromal cells and the mechanics of the microenvironment have emerged as important themes in driving invasion and metastasis. While current anti-melanoma therapies target either the MAPK signaling pathway or immune checkpoints, there are no drugs available that specifically inhibit motility and thus invasion and dissemination of melanoma cells during metastasis. One of the reasons for the lack of so-called “migrastatics” is that, despite decades of research, the precise biology of metastatic disease is still not fully understood. Metastatic disease has been traditionally lumped into a single classification, however what is now emergent is that the biology of melanoma metastasis is highly diverse, heterogeneous and exceedingly dynamic—suggesting that not all cases are created equal. The following mini-review discusses melanoma heterogeneity in the context of the emergent theme of mechanobiology and how it influences the tumor-stroma crosstalk during metastasis. Thus, highlighting future therapeutic options for migrastatics and mechanomedicines in the prevention and treatment of metastatic melanoma.

【 授权许可】

Unknown