Background: The introduction of cART has changed the morbidity and mortality patterns affecting HIV-infected (HIV+)individuals. The risk of breast cancer in HIV+ patients has now approached the general population risk. However, breastcancer has a more aggressive clinical course and poorer outcome in HIV+ patients than in general population, withoutcorrelation with the CD4 or virus particles count. These findings suggest a likely influence of HIV-1 proteins on breast canceraggressiveness and progression. The HIV-1 matrix protein (p17) is expressed in different tissues and organs of successfullycART-treated patients and promotes migration of different cells. Variants of p17 (vp17s), characterized by mutations andamino acid insertions, differently from the prototype p17 (refp17), also promote B-cell proliferation and transformation.Methods: Wound-healing assay, matrigel-based invasion assay, and anchorage-independent proliferation assay wereemployed to compare the biological activity exerted by refp17 and three different vp17s on the triple-negative humanbreast cancer cell line MDA-MB 231. Intracellular signaling was investigated by western blot analysis.Results: Motility and invasiveness increased in cells treated with both refp17 and vp17s compared to untreated cells. Theeffects of the viral proteins were mediated by binding to the chemokine receptor CXCR2 and activation of the ERK1/2signaling pathway. However, vp17s promoted MDA-MB 231 cell growth and proliferation in contrast to refp17-treated ornot treated cells.Conclusions: In the context of the emerging role of the microenvironment in promoting and supporting cancer cellgrowth and metastatic spreading, here we provide the first evidence that exogenous p17 may play a crucial role insustaining breast cancer cell migration and invasiveness, whereas some p17 variants may also be involved in cancer cellgrowth and proliferation.
HIV-1 matrix protein p17 and its variants promote human triple negative breast cancer cell aggressiveness / Caccuri, F; Giordano, Francesca; Barone, I; Mazzuca, P; Giagulli, C; Andò, S; Caruso, A; Marsico, Stefania. - In: INFECTIOUS AGENTS AND CANCER. - ISSN 1750-9378. - (2017).
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|Titolo:||HIV-1 matrix protein p17 and its variants promote human triple negative breast cancer cell aggressiveness|
|Data di pubblicazione:||2017|
|Citazione:||HIV-1 matrix protein p17 and its variants promote human triple negative breast cancer cell aggressiveness / Caccuri, F; Giordano, Francesca; Barone, I; Mazzuca, P; Giagulli, C; Andò, S; Caruso, A; Marsico, Stefania. - In: INFECTIOUS AGENTS AND CANCER. - ISSN 1750-9378. - (2017).|
|Appare nelle tipologie:||1.1 Articolo in rivista|