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

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 co...

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Autores principales: Hayasaka, Haruko, Yoshida, Junichi, Kuroda, Yasutaka, Nishiguchi, Akihiro, Matsusaki, Michiya, Kishimoto, Kei, Nishimura, Hitoshi, Okada, Mari, Shimomura, Yuki, Kobayashi, Daichi, Shimazu, Yoshihito, Taya, Yuji, Akashi, Mitsuru, Miyasaka, Masayuki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990860/
https://www.ncbi.nlm.nih.gov/pubmed/35133060
http://dx.doi.org/10.1111/cas.15293
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author Hayasaka, Haruko
Yoshida, Junichi
Kuroda, Yasutaka
Nishiguchi, Akihiro
Matsusaki, Michiya
Kishimoto, Kei
Nishimura, Hitoshi
Okada, Mari
Shimomura, Yuki
Kobayashi, Daichi
Shimazu, Yoshihito
Taya, Yuji
Akashi, Mitsuru
Miyasaka, Masayuki
author_facet Hayasaka, Haruko
Yoshida, Junichi
Kuroda, Yasutaka
Nishiguchi, Akihiro
Matsusaki, Michiya
Kishimoto, Kei
Nishimura, Hitoshi
Okada, Mari
Shimomura, Yuki
Kobayashi, Daichi
Shimazu, Yoshihito
Taya, Yuji
Akashi, Mitsuru
Miyasaka, Masayuki
author_sort Hayasaka, Haruko
collection PubMed
description 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(+) intratumoral and peritumoral lymphatic vessels. In the three‐dimensional tumor invasion model with lymph networks, CXCL12 stimulation facilitates breast cancer cell migration to CCL21‐reconstituted lymphatic networks. These results indicate that CXCL12/CXCR4 signaling promotes breast cancer cell migration and invasion toward CCR7 ligand–expressing intratumoral lymphatic vessels and supports CCR7 signaling associated with lymph node metastasis.
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spelling pubmed-89908602022-04-13 CXCL12 promotes CCR7 ligand–mediated breast cancer cell invasion and migration toward lymphatic vessels Hayasaka, Haruko Yoshida, Junichi Kuroda, Yasutaka Nishiguchi, Akihiro Matsusaki, Michiya Kishimoto, Kei Nishimura, Hitoshi Okada, Mari Shimomura, Yuki Kobayashi, Daichi Shimazu, Yoshihito Taya, Yuji Akashi, Mitsuru Miyasaka, Masayuki Cancer Sci ORIGINAL ARTICLES 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(+) intratumoral and peritumoral lymphatic vessels. In the three‐dimensional tumor invasion model with lymph networks, CXCL12 stimulation facilitates breast cancer cell migration to CCL21‐reconstituted lymphatic networks. These results indicate that CXCL12/CXCR4 signaling promotes breast cancer cell migration and invasion toward CCR7 ligand–expressing intratumoral lymphatic vessels and supports CCR7 signaling associated with lymph node metastasis. John Wiley and Sons Inc. 2022-02-14 2022-04 /pmc/articles/PMC8990860/ /pubmed/35133060 http://dx.doi.org/10.1111/cas.15293 Text en © 2022 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle ORIGINAL ARTICLES
Hayasaka, Haruko
Yoshida, Junichi
Kuroda, Yasutaka
Nishiguchi, Akihiro
Matsusaki, Michiya
Kishimoto, Kei
Nishimura, Hitoshi
Okada, Mari
Shimomura, Yuki
Kobayashi, Daichi
Shimazu, Yoshihito
Taya, Yuji
Akashi, Mitsuru
Miyasaka, Masayuki
CXCL12 promotes CCR7 ligand–mediated breast cancer cell invasion and migration toward lymphatic vessels
title CXCL12 promotes CCR7 ligand–mediated breast cancer cell invasion and migration toward lymphatic vessels
title_full CXCL12 promotes CCR7 ligand–mediated breast cancer cell invasion and migration toward lymphatic vessels
title_fullStr CXCL12 promotes CCR7 ligand–mediated breast cancer cell invasion and migration toward lymphatic vessels
title_full_unstemmed CXCL12 promotes CCR7 ligand–mediated breast cancer cell invasion and migration toward lymphatic vessels
title_short CXCL12 promotes CCR7 ligand–mediated breast cancer cell invasion and migration toward lymphatic vessels
title_sort cxcl12 promotes ccr7 ligand–mediated breast cancer cell invasion and migration toward lymphatic vessels
topic ORIGINAL ARTICLES
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8990860/
https://www.ncbi.nlm.nih.gov/pubmed/35133060
http://dx.doi.org/10.1111/cas.15293
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