Surgical Treatment of Osteosarcoma Induced Distant Pre‐Metastatic Niche in Lung to Facilitate the Colonization of Circulating Tumor Cells

Abstract

Recently, the major challenge in treating osteosarcoma patients is the metastatic disease, most commonly in the lungs. However, the underlying mechanism of recurrence and metastasis of osteosarcoma after surgical resection of primary tumor remains unclear. This study aims to investigate whether the pulmonary metastases characteristic of osteosarcoma is associated with surgical treatment and whether surgery contributes to the formation of pre‐metastatic niche in the distant lung tissue. In the current study, the authors observe the presence of circulating tumor cells in patients undergoing surgical resection of osteosarcoma which is correlated to tumor recurrence. The pulmonary infiltrations of neutrophils and Gr‐1+ myeloid cells are characterized to form a pre‐metastatic niche upon the exposure of circulating tumor cells after surgical resection. It is found that mitochondrial damage‐associated molecular patterns released from surgical resection contribute to the formation of pre‐metastatic niche in lung through IL‐1β secretion. This study reveals that surgical management for osteosarcoma, irrespective of the primary tumor, might promote the formation of postoperative pre‐metastatic niche in lung which is with important implications for developing rational therapies during peri‐operative period.

Metastasis-initiating osteosarcoma subpopulations establish paracrine interactions with both lung and tumor cells to create a metastatic niche

“…Utilizing a novel combinatorial approach of experimental in vivo platforms (Primary-No Primary, Early amputation, Red-green), we provide evidence to support that primary tumors influence circulating tumor cell fate and impair lung colonization, which agrees with recent findings from other groups[34, 35]. We significantly add to this growing body of literature, finding that in the presence of micro-metastatic disease, circulating tumor cells overwhelmingly favored recruitment to the established micro-metastatic lesions over initiating new ones.…”

Exosome-mediated mechanisms in lung cancer metastasis and advancements in medical submission: A comprehensive review

“…Stages 2 and 3 represent moderate levels. Through the production of growth hormones and cytokines, it has been shown that tumor cells play a pivotal function in guiding cells originating from the bone marrow (Tang et al 2023) toward potential metastatic locations, hence fostering the creation of pre-metastatic niches that support tumor growth. Furthermore, it has become clear that two critical factors controlling pre-metastatic areas are hypoxia induction inside the primary tumor and tumor-derived exosomes.…”