CXCL12 promotes CCR7 ligand–mediated breast cancer cell invasion and migration toward lymphatic vessels

Autor: Haruko Hayasaka, Junichi Yoshida, Yasutaka Kuroda, Akihiro Nishiguchi, Michiya Matsusaki, Kei Kishimoto, Hitoshi Nishimura, Mari Okada, Yuki Shimomura, Daichi Kobayashi, Yoshihito Shimazu, Yuji Taya, Mitsuru Akashi, Masayuki Miyasaka
Rok vydání: 2022
Předmět:
Zdroj: Cancer Science. 113:1338-1351
ISSN: 1349-7006
1347-9032
DOI: 10.1111/cas.15293
Popis: Chemokines are a family of cytokines that mediate leukocyte trafficking and are involved in tumor cell migration, growth, and progression. Although there is emerging evidence that multiple chemokines are expressed in tumor tissues and that each chemokine induces receptor-mediated signaling, their collaboration to regulate tumor invasion and lymph node metastasis has not been fully elucidated. In this study, we examined the effect of CXCL12 on the CCR7-dependent signaling in MDA-MB-231 human breast cancer cells to determine the role of CXCL12 and CCR7 ligand chemokines in breast cancer metastasis to lymph nodes. CXCL12 enhanced the CCR7-dependent in vitro chemotaxis and cell invasion into collagen gels at suboptimal concentrations of CCL21. CXCL12 promoted CCR7 homodimer formation, ligand binding, CCR7 accumulation into membrane ruffles, and cell response at lower concentrations of CCL19. Immunohistochemistry of MDA-MB-231-derived xenograft tumors revealed that CXCL12 is primarily located in the pericellular matrix surrounding tumor cells, whereas the CCR7 ligand, CCL21, mainly associates with LYVE-1
Databáze: OpenAIRE
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