Department of Interdisciplinary Medicine, "Aldo Moro" University of Bari, Bari, Italy.
INBB, National Institute for Biostructures and Biosystems, 00136, Rome, Italy.
Commun Biol. 2022 Jun 7;5(1):553. doi: 10.1038/s42003-022-03486-7.
Several studies highlighted the importance of platelets in the tumor microenvironment due to their ability to interact with other cell types such as leukocytes, endothelial, stromal and cancer cells. Platelets can influence tumor development and metastasis formation through several processes consisting of the secretion of growth factors and cytokines and/or via direct interaction with cancer cells and endothelium. Patients with visceral obesity (VO) are susceptible to pro-thrombotic and pro-inflammatory states and to development of cancer, especially colon cancer. These findings provide us with the impetus to analyze the role of platelets isolated from VO patients in tumor growth and progression with the aim to explore a possible link between platelet activation, obesity and colon cancer. Here, using xenograft colon cancer models, we prove that platelets from patients with visceral obesity are able to strongly promote colon cancer growth. Then, sequencing platelet miRNome, we identify miR-19a as the highest expressed miRNA in obese subjects and prove that miR-19a is induced in colon cancer. Last, administration of miR-19a per se in the xenograft colon cancer model is able to promote colon cancer growth. We thus elect platelets with their specific miRNA abundance as important factors in the tumor promoting microenvironment of patients with visceral obesity.
多项研究强调了血小板在肿瘤微环境中的重要性,因为它们能够与白细胞、内皮细胞、基质和癌细胞等其他细胞类型相互作用。血小板可以通过多种过程影响肿瘤的发展和转移的形成,这些过程包括生长因子和细胞因子的分泌,以及/或者通过与癌细胞和内皮细胞的直接相互作用。内脏肥胖(VO)患者易发生血栓形成和炎症前状态,并易发生癌症,尤其是结肠癌。这些发现促使我们分析从 VO 患者中分离出的血小板在肿瘤生长和进展中的作用,目的是探索血小板激活、肥胖和结肠癌之间的可能联系。在这里,我们使用异种移植结肠癌模型证明,内脏肥胖患者的血小板能够强烈促进结肠癌的生长。然后,对血小板 microRNA 组进行测序,我们确定 miR-19a 是肥胖患者中表达最高的 miRNA,并证明 miR-19a 在结肠癌中被诱导。最后,在异种移植结肠癌模型中单独给予 miR-19a,能够促进结肠癌的生长。因此,我们选择具有特定 microRNA 丰度的血小板作为内脏肥胖患者肿瘤促进微环境中的重要因素。