Although malignant melanoma is the less frequently diagnosed skin cancer, it shows a poor prognosis due its chemoresistance and metastasis development. One of the acquired abilities of transformed cells is anoikis resistance and this property is closely related to metastasis formation. To acquire the ability to form metastases, cells must survive independently of interactions with the extracellular matrix and thus resist to anoikis. In this way, the study of changes that occur in tumor cells that acquire this ability is of great relevance. In our laboratory, we developed a model that allows us to study different stages of the genesis of melanoma. Murine melan-a melanocytes that survived after 1, 2, 3 and 4 deadhesion cycles for 96 hours showed changes in morphology and growth independent of phorbol myristate acetate (PMA), and were termed 1C, 2C, 3C and 4C, respectively. Different melanoma cell lines (4C11-, 4C11+, Tm1, Tm5, etc.) were established after submitting the surviving spheroids of 4C cell line to limiting dilution. Previous data from our laboratory demonstrated increased expression of Timp1 and resistance to anoikis during the malignant transformation of melanocytes. Melan-a melanocytes overexpressing Timp1 acquire anoikis-resistant phenotype. In our laboratory, we observed interaction between CD63, Timp1 and b1-integrin in the 4C, 4C11- and 4C11+ cell lines established after cycles of anchorage impediment. This seems to be the first study describing the interaction between Timp1, CD63 and b1-integrin in tumor cells. However, it is unclear how Timp1 modulates resistance to anoikis. Therefore, our aim is to analyze the role of Timp1 in the context of Timp1/CD63 / b1-integrin complex and the signaling pathways involved in the acquisition of anoikis resistance.
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