Browsing by Author "Vera, Tamara"
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Item Exosomes released upon mitochondrial ASncmtRNA knockdown reduce tumorigenic properties of malignant breast cancer cells.(Nature Publishing Group, 2020) Lobos-González, Lorena; Bustos, Rocío; Campos, América; Silva, Valeria; Silva, Verónica; Jeldes, Emanuel; Salomon, Carlos; Varas-Godoy, Manuel; Cáceres-Verschae, Albano; Durán, Eduardo; Vera, Tamara; Ezquer, Fernando; Ezquer, Marcelo; Burzio, Verónica; Villegas, JaimeDuring intercellular communication, cells release extracellular vesicles such as exosomes, which contain proteins, ncRNAs and mRNAs that can influence proliferation and/or trigger apoptosis in recipient cells, and have been proposed to play an essential role in promoting invasion of tumor cells and in the preparation of metastatic niches. Our group proposed the antisense non-coding mitochondrial RNA (ASncmtRNA) as a new target for cancer therapy. ASncmtRNA knockdown using an antisense oligonucleotide (ASO-1537S) causes massive death of tumor cells but not normal cells and strongly reduces metastasis in mice. In this work, we report that exosomes derived from ASO-1537S-treated MDA-MB-231 breast cancer cells (Exo-1537S) inhibits tumorigenesis of recipient cells, in contrast to exosomes derived from control-ASO-treated cells (Exo-C) which, in contrast, enhance these properties. Furthermore, an in vivo murine peritoneal carcinomatosis model showed that Exo-1537S injection reduced tumorigenicity compared to controls. Proteomic analysis revealed the presence of Lactadherin and VE-Cadherin in exosomes derived from untreated cells (Exo-WT) and Exo-C but not in Exo-1537S, and the latter displayed enrichment of proteasomal subunits. These results suggest a role for these proteins in modulation of tumorigenic properties of exosome-recipient cells. Our results shed light on the mechanisms through which ASncmtRNA knockdown affects the preparation of breast cancer metastatic niches in a peritoneal carcinomatosis model.Item Lactadherin: From a Well-Known Breast Tumor Marker to a Possible Player in Extracellular Vesicle-Mediated Cancer Progression(2022) Durán, Eduardo; Vera, Tamara; Lobos-González, LorenaLactadherin is a secreted glycoprotein associated with the milk fat globule membrane, which is highly present in the blood and in the mammary tissue of lactating women. Several biological functions have been associated with this protein, mainly attributable to its immunomodulatory role promoting phagocyte-mediated clearance of apoptotic cells. It has been shown that lactadherin also plays important roles in cell adhesion, the promotion of angiogenesis, and tissue regeneration. On the other hand, this protein has been used as a marker of breast cancer and tumor progression. Recently, high levels of lactadherin has been associated with poor prognosis and decreased survival, not only in breast cancer, but also in melanoma, ovarian, colorectal, and other types of cancer. Although the mechanisms responsible for the tumor-promoting effects attributed to lactadherin have not been fully elucidated, a growing body of literature indicates that lactadherin could be a promising therapeutic target and/or biomarker for breast and other tumors. Moreover, recent studies have shown its presence in extracellular vesicles derived from cancer cell lines and cancer patients, which was associated with cancer aggressiveness and worse prognosis. Thus, this review will focus on the link between lactadherin and cancer development and progression, its possible use as a cancer biomarker and/or therapeutic target, concluding with a possible role of this protein in cellular communication mediated by extracellular vesicles.vo model for surgical resection procedures in cancer research.