Exosomes are cell-secreted microvesicles that play important roles in epithelial ovarian cancer (EOC) progression, as they are constantly secreted into ascites fluids. While cells spontaneously release exosomes, alterations in intracellular calcium or extracellular pH can release additional exosomes. Yet, little is known about how these exosomes compare to those that are continuously released without stimulation and how they mediate cellular activities important in cancer progression. Here, we demonstrate that chelation of extracellular calcium leads to release of chelation-induced exosomes (CI-exosomes) from OVCAR-3 EOC cells. CI-exosomes display a unique miRNA profile compared to naturally secreted exosomes (SEC-exosomes). Furthermore, treatment with CI- and SEC-exosomes leads to differential biophysical and functional changes including, adhesion and migration in EOC-derived fibroblasts that suggest the development of a malignant tumor microenvironment. This result highlights how tumor environmental factors contribute to heterogeneity in exosome populations and how different exosome populations mediate diversity in stromal cell behavior.

外泌体是细胞分泌的微泡，由于它们不断分泌到腹水中，因此它们在上皮性卵巢癌（EOC）进展中起重要作用。当细胞自发释放外泌体时，细胞内钙或细胞外pH的改变会释放出其他外泌体。然而，关于这些外泌体与不经刺激连续释放的外泌体的比较，以及它们如何介导对癌症进展重要的细胞活性，鲜为人知。在这里，我们证明了细胞外钙的螯合导致从OVCAR-3 EOC细胞释放螯合诱导的外泌体（CI-外泌体）。与自然分泌的外泌体（SEC外泌体）相比，CI外泌体显示出独特的miRNA谱。此外，用CI和SEC外泌体进行治疗会导致生物物理和功能的差异变化，其中包括：EOC来源的成纤维细胞中的黏附和迁移提示恶性肿瘤微环境的发展。该结果突出了肿瘤环境因素如何促进外泌体群体的异质性，以及不同的外泌体群体如何介导基质细胞行为的多样性。