Avaliação do papel da pentraxina 3 na biologia de células tumorais humanas

Abstract

Melanoma is a type of cancer characterized by malignant transformation of melanocytes. Different types of molecular factors have been depicted as being important for melanoma progression, such as overexpression of pro-proliferative factors (VEGFA, EGF), changes in the expression of proto-oncogenes and microRNAs related to melanoma progression and constitutive activation of signaling pathways such as PI3K-AKT. Fibroblast growth factors (FGF) are key molecules in tumor progression by promoting cell proliferation and angiogenesis through interaction with receptor tyrosine kinases (FGFRs). The long pentraxin PTX3 interacts with FGF2, inhibiting the pro-tumor actions induced by this factor. Therefore, PTX3 is a promising therapeutic tool in delaying the progression of several tumors, including melanomas. This study aimed to investigate the biological effect of recombinant human PTX3 protein (rhPTX3) on important biological traits for tumor progression in cell lines constitutively expressing FGF2 and FGFR4 derived from human fibrosarcoma tumors (HT-1080), colorectal adenocarcinoma (HCT-116) and malignant melanoma (SK-Mel-37 and SK-Mel-188). Our data showed that treatment with rhPTX3 inhibited cell proliferation, cell colonies formation ability and cell migration of SK-Mel-188 and SK-Mel-37 melanomas. Analyzes of gene expression by RT-qPCR showed that PTX3 also modulated the expression of FGF2, FGFBP and FGFR4 and that in vivo tumorigenesis of PTX3-transfected SK-Mel-37 cells was inhibited. Preliminary data show that PTX3 can modulate the expression of microRNAs associated with melanomas progression, such as miR-149 and miR-188. Our data suggest that PTX3 interferes in important tumor cell characteristics that may compromise the progression of melanomas, however, its potential as a tumor progression biomarker or even its use in the therapy of this type of malignancy needs to be further studied.