Rodríguez Marta, Silva Javier, Herrera Alberto, Herrera Mercedes, Peña Cristina, Martín Paloma, Gil-Calderón Beatriz, Larriba María Jesús, Coronado M Josés, Soldevilla Beatriz, Turrión Víctor S, Provencio Mariano, Sánchez Antonio, Bonilla Félix, García-Barberán Vanesa
"Mecanismos Moleculares Tumorales" Research Group, Department of Medical Oncology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain.
"Señalización Celular en Cáncer" Research Group, Department of Medical Oncology, IDIPHIM, Instituto de Investigación Sanitaria Puerta de Hierro, Madrid, E-28222, Spain.
Oncotarget. 2015 Dec 1;6(38):40575-87. doi: 10.18632/oncotarget.5818.
Cancer cells efficiently transfer exosome contents (essentially mRNAs and microRNAs) to other cell types, modifying immune responses, cell growth, angiogenesis and metastasis. Here we analyzed the exosomes release by breast tumor cells with different capacities of stemness/metastasis based on CXCR4 expression, and evaluated their capacity to generate oncogenic features in recipient cells. Breast cancer cells overexpressing CXCR4 showed an increase in stemness-related markers, and in proliferation, migration and invasion capacities. Furthermore, recipient cells treated with exosomes from CXCR4-cells showed increased in the same abilities. Moreover, inoculation of CXCR4-cell-derived exosomes in immunocompromised mice stimulated primary tumor growth and metastatic potential. Comparison of nucleic acids contained into exosomes isolated from patients revealed a "stemness and metastatic" signature in exosomes of patients with worse prognosis. Finally, our data supported the view that cancer cells with stem-like properties show concomitant metastatic behavior, and their exosomes stimulate tumor progression and metastasis. Exosomes-derived nucleic acids from plasma of breast cancer patients are suitable markers in the prognosis of such patients.
癌细胞能有效地将外泌体内容物（主要是mRNA和微小RNA）转移到其他细胞类型中，从而改变免疫反应、细胞生长、血管生成和转移。在此，我们基于CXCR4表达分析了具有不同干性/转移能力的乳腺肿瘤细胞释放的外泌体，并评估了它们在受体细胞中产生致癌特征的能力。过表达CXCR4的乳腺癌细胞在干性相关标志物以及增殖、迁移和侵袭能力方面均有所增加。此外，用来自CXCR4 +细胞的外泌体处理的受体细胞在相同能力方面也有所增强。此外，在免疫缺陷小鼠中接种CXCR4 +细胞来源的外泌体可刺激原发性肿瘤生长和转移潜能。对从患者分离的外泌体中所含核酸的比较揭示了预后较差患者外泌体中的“干性和转移”特征。最后，我们的数据支持了具有干细胞样特性的癌细胞表现出伴随的转移行为，且其外泌体刺激肿瘤进展和转移的观点。乳腺癌患者血浆中源自外泌体的核酸是此类患者预后的合适标志物。
