Abstract
CD271 is a neurotrophin receptor variably expressed in melanoma. Although contradictory data are reported on its role as a marker of tumor-initiating cells, little is known about its function in tumor progression. CD271 expression was higher in spheroids derived from freshly isolated cells of primary melanomas and in primary WM115 and WM793-B cell lines, and it decreased during progression to advanced stages in cells isolated from metastatic melanomas and in metastatic WM266-4 and 1205Lu cell lines. Moreover, CD271 was scarcely detected in the highly invasive spheroids (SKMEL28 and 1205Lu). CD271, originally expressed in the epidermis of skin reconstructs, disappeared when melanoma started to invade the dermis. SKMEL8 CD271(-) cells showed greater proliferation and invasiveness invitro and were associated with a higher number of metastases in zebrafish compared with CD271(+) cells. CD271 silencing in WM115 induced a more aggressive phenotype invitro and invivo. On the contrary, CD271 overexpression in SKMEL28 cells reduced invasion invitro, and CD271 overexpressing 1205Lu cells was associated with a lower percentage of metastases in zebrafish. A reduced cell-cell adhesion was also observed in the absence of CD271. Taken together, these results indicate that CD271 loss is critical for melanoma progression and metastasis.
Highlights
Melanoma is the deadliest type of skin cancer, and its incidence is rising faster than that of any other solid tumor (Eggermont et al, 2014)
We recently showed that CD271 is markedly expressed in early-stage melanomas and that it is progressively lost during tumor progression, showing an inverse correlation with hypoxia inducible factor-1 (HIF-1a) (Marconi et al, 2015)
CD271 expression was evaluated in long-standing cell lines (WM115, WM266-4, SKMEL28, WM793-B, and 1205Lu) derived from melanomas of different stages and in cells freshly isolated from a primary melanoma (PM) and a metastatic melanoma (MM)
Summary
Melanoma is the deadliest type of skin cancer, and its incidence is rising faster than that of any other solid tumor (Eggermont et al, 2014). We have previously shown that melanoma cells express neurotrophins and their receptors and play a role in tumor progression (Truzzi et al, 2008). CD271 was first isolated from a melanoma cell line and is expressed on neural crest cells, from which melanocytes are derived (Kruger et al, 2002) It belongs to the tumor necrosis factor receptor superfamily and mediates apoptosis in different cell settings via its own signaling pathway (Blochl and Bloch, 2007; Kraemer et al, 2014; Truzzi et al, 2011). We show a reduced expression of b1-integrin and decreased cell-cell adhesion in the absence of CD271, resulting in poor tumor cell adhesion and in a greater predisposition to invade the microenvironment
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