Vannini Ivan, Urbini Milena, Melloni Mattia, Rossi Tania, Gallerani Giulia, Palleschi Michela, Azzali Irene, Puccetti Maurizio, Martinelli Giovanni, Fabbri Francesco
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori (IRST) "Dino Amadori", Meldola, Italy.
Laboratory of Biomarkers, Biomolecular Targets and Personalized Medicine in Oncology, Translational Medicine, University of Ferrara, Ferrara, Italy.
Front Med (Lausanne). 2022 Mar 9;9:827206. doi: 10.3389/fmed.2022.827206. eCollection 2022.
Metaplastic breast cancer (MpBC) is a rare tumor representing 1% of all breast malignancies. The prognosis of this histologic subtype is actually poor and there are no current clear-cut therapeutic guidelines. Hence, despite its uniqueness, its aggressive prognostic profile strongly encourages further studies to identify new markers and therapeutic targets. Herein, we report a case of 32-years-old patient affected with of triple negative spindle-shaped MpBC. The research of molecular targets on the primary tumor did not allow performing an effective therapeutic choice. Extracellular Vesicles (EVs) are under intense study as new potential pathophysiological markers and targets for therapeutic applications, in different tumors for their role in tumor onset, progression and aggressiveness. Here, we examined the involvement of EVs in this case, to look into the MpBC microenvironment willing to identify new potential molecular targets, pathways of aggressiveness, and markers of prognosis and therapeutic efficacy. Firstly, we characterized MpBC patient EV dimensions and surface proteins. Moreover, we analyzed the EV RNA cargo supposed to be delivered to nearby and distant recipient cells. Interestingly, we observed a dysregulation EV-contained miRNAs, which could determine an increased expression of oncogenes in the tumor microenvironment, probably enabling cancer progression. These data suggest that the characterization of miRNA cargo of EVs could be important for the identification of new markers and for the application of future new target therapies.
化生性乳腺癌（MpBC）是一种罕见肿瘤，占所有乳腺恶性肿瘤的1%。这种组织学亚型的预后实际上很差，目前尚无明确的治疗指南。因此，尽管它具有独特性，但其侵袭性的预后特征强烈鼓励进一步开展研究以确定新的标志物和治疗靶点。在此，我们报告一例32岁患有三阴性梭形MpBC的患者。对原发肿瘤的分子靶点研究未能做出有效的治疗选择。细胞外囊泡（EVs）作为新的潜在病理生理标志物和治疗应用靶点正受到深入研究，因其在不同肿瘤的发生、进展和侵袭性中发挥作用。在此，我们研究了EVs在该病例中的作用，以探究MpBC微环境，旨在确定新的潜在分子靶点、侵袭途径以及预后和治疗疗效标志物。首先，我们对MpBC患者的EVs尺寸和表面蛋白进行了表征。此外，我们分析了预计会递送至附近和远处受体细胞的EV RNA货物。有趣的是，我们观察到EVs中所含miRNA存在失调，这可能会导致肿瘤微环境中癌基因表达增加，可能促使癌症进展。这些数据表明，对EVs的miRNA货物进行表征对于确定新的标志物以及未来新的靶向治疗的应用可能具有重要意义。
