Self-seeding circulating tumor cells promote the proliferation and metastasis of human osteosarcoma by upregulating interleukin-8

Cell Death & Disease
Tao LiuXiuchun Qiu

Abstract

Most circulating tumor cells (CTCs) die during the process of metastasis, but self-seeding CTCs can invade the primary tumor or form clinically meaningful metastases. This study aimed to evaluate the capacity of self-seeding CTCs to promote osteosarcoma growth and lung metastasis and to clarify the specific role of interleukin (IL)-8 in CTC self-seeding. We successfully isolated and cultured self-seeding CTCs through a self-seeding nude mouse model established using green fluorescent protein (GFP)-labeled F5M2 cells and found that self-seeding CTCs exhibit increased cellular proliferation, migration, and invasion in vitro, increased tumor growth and lung metastasis in mice, and increased IL-8 expression. Furthermore, suppressing IL-8 inhibited tumor growth and metastasis and reduced CTC seeding in primary tumors in vitro and in vivo. In osteosarcoma patients, IL-8 levels significantly correlated with the Enneking stage and metastasis. These findings demonstrate that self-seeding osteosarcoma CTCs can promote tumor growth and lung metastasis through IL-8. Their increased metastatic potential and elevated IL-8 expression suggest a novel strategy for future therapeutic interventions to prevent osteosarcoma progression and metastasis.

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Citations

Jan 25, 2021·BMC Molecular and Cell Biology·Liqing WangChangxin Wu
Mar 23, 2021·Frontiers in Oncology·Daria KlusaClaudia Peitzsch
Jul 22, 2021·Current Cancer Drug Targets·Gening Snezhanna OGening Tatyana P

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Methods Mentioned

BETA
fluorescence imaging
Laser capture microdissection
Enzyme-linked immunosorbent assay
transfection
ELISA
PCR
fluorescence microscopy

Software Mentioned

GraphPad Prism
GraphPad

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