Premetastatic niches, exosomes and circulating tumor cells: Early mechanisms of tumor dissemination and the relation to surgery

Abstract

The physiological stress response to surgery promotes wound healing and functional recovery and includes the activation of neural, inflammatory and proangiogenic signaling pathways. Paradoxically, the same pathways also promote metastatic spread and growth of residual cancer. Human and animal studies show that cancer surgery can increase survival, migration and proliferation of residual tumor cells. To secure the survival and growth of disseminated tumor cells, the formation of premetastatic niches in target organs involves a complex interplay between microenvironment, immune system, circulating tumor cells, as well as chemical mediators and exosomes secreted by the primary tumor. This review describes the current understanding of the early mechanisms of dissemination, as well as how surgery may facilitate disease progression.

Molecular principles of metastasis: a hallmark of cancer revisited

“…Some cells undergo dormancy as an adaptation mechanism to the new stressful environment either extravasate by transendothelial migration or grow within the vessel before eventual extravasation and colonization of the PMN. [194][195][196][197] Do circulating tumor cells interact with immune cells? CTCs must adapt to the strict selective environment present in the lumen of the vasculature.…”

Cancer-Associated Fibroblasts and Tumor-Associated Macrophages in Cancer and Cancer Immunotherapy

“…Inflammatory mediators such as TGF-β, interleukin (IL)-1, and IL-6 produced by tumor cells and non-malignant stromal cells promote CAF activation and contribute to a pro-inflammatory profile, that directly support carcinogenesis ( 16 ). The activation of specific transcriptional programs and the lack of negative feedback mechanisms launch CAF into self-sustaining trajectories ( 17 , 18 ).…”

Clinical Implications of Exosomes: Targeted Drug Delivery for Cancer Treatment

“…Exosomes can enhance metastasis by enhancing EMT, promoting cell proliferation, or even degrading the ECM to promote cell invasion and metastasis from the primary site [ 24 ]. For example, recent work from Wang et al demonstrated how cancer-associated fibroblast exosomes could transfer miR-181-5p to breast cancer cells, which inhibited CDX2 and led to an acceleration of EMT [ 25 ].…”