The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes

Guérard, Adrien; Laurent, Victor; Fromont, Gaëlle; Estève, David; Gilhodes, Julia; Bonnelye, Edith; Le Gonidec, Sophie; Valet, Philippe; Malavaud, Bernard; Reina, Nicolas; Attané, Camille; Muller, Catherine

doi:10.3390/ijms22041994

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The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes

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^1,* and

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Institut de Pharmacologie et de Biologie Structurale (IPBS), Université de Toulouse, CNRS UMR 5089, 205 Route de Narbonne, 31077 Toulouse, France

Service d’Anatomie Pathologique, CHRU de Tours, Inserm UMR 1069, 37000 Tours, France

Département de Biostatistiques, Institut Universitaire du Cancer, CEDEX 9, 31059 Toulouse, France

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Lyos, INSERM, UMR1033, 69008 Lyon, France

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Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), INSERM U1048, Université de Toulouse, 31432 Toulouse, France

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Département d’Urologie, Institut Universitaire du Cancer, CEDEX 9, 31059 Toulouse, France

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Service de Traumatologie et de Chirurgie Orthopédique, CHU de Toulouse—Purpan, 31059 Toulouse, France

Authors to whom correspondence should be addressed.

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Current Address: CNRS ERL 6001/ INSERM U1232, 44805 Saint-Herblain, France.

^‡

Current Adrress: RESTORE Institute, UMR 1301 Inserm—5070 CNRS—Université de Toulouse, 1100 Toulouse, France.

Academic Editor: Michele Caraglia

Int. J. Mol. Sci. 2021, 22(4), 1994; https://doi.org/10.3390/ijms22041994

Received: 10 December 2020 / Revised: 4 February 2021 / Accepted: 12 February 2021 / Published: 17 February 2021

(This article belongs to the Special Issue Attacking Cancer Progression and Metastasis 2.0)

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Abstract

Bone metastasis remains the most frequent and the deadliest complication of prostate cancer (PCa). Mechanisms leading to the homing of tumor cells to bone remain poorly characterized. Role of chemokines in providing navigational cues to migrating cancer cells bearing specific receptors is well established. Bone is an adipocyte-rich organ since 50 to 70% of the adult bone marrow (BM) volume comprise bone marrow adipocytes (BM-Ads), which are likely to produce chemokines within the bone microenvironment. Using in vitro migration assays, we demonstrated that soluble factors released by human primary BM-Ads are able to support the directed migration of PCa cells in a CCR3-dependent manner. In addition, we showed that CCL7, a chemokine previously involved in the CCR3-dependent migration of PCa cells outside of the prostate gland, is released by human BM-Ads. These effects are amplified by obesity and ageing, two clinical conditions known to promote aggressive and metastatic PCa. In human tumors, we found an enrichment of CCR3 in bone metastasis vs. primary tumors at mRNA levels using Oncomine microarray database. In addition, immunohistochemistry experiments demonstrated overexpression of CCR3 in bone versus visceral metastases. These results underline the potential importance of BM-Ads in the bone metastatic process and imply a CCR3/CCL7 axis whose pharmacological interest needs to be evaluated. View Full-Text

Keywords: prostate cancer; bone metastasis; bone marrow adipocytes; CCR3; chemokine

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Guérard, A.; Laurent, V.; Fromont, G.; Estève, D.; Gilhodes, J.; Bonnelye, E.; Le Gonidec, S.; Valet, P.; Malavaud, B.; Reina, N.; Attané, C.; Muller, C. The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes. Int. J. Mol. Sci. 2021, 22, 1994. https://doi.org/10.3390/ijms22041994

AMA Style

Guérard A, Laurent V, Fromont G, Estève D, Gilhodes J, Bonnelye E, Le Gonidec S, Valet P, Malavaud B, Reina N, Attané C, Muller C. The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes. International Journal of Molecular Sciences. 2021; 22(4):1994. https://doi.org/10.3390/ijms22041994

Chicago/Turabian Style

Guérard, Adrien, Victor Laurent, Gaëlle Fromont, David Estève, Julia Gilhodes, Edith Bonnelye, Sophie Le Gonidec, Philippe Valet, Bernard Malavaud, Nicolas Reina, Camille Attané, and Catherine Muller. 2021. "The Chemokine Receptor CCR3 Is Potentially Involved in the Homing of Prostate Cancer Cells to Bone: Implication of Bone-Marrow Adipocytes" International Journal of Molecular Sciences 22, no. 4: 1994. https://doi.org/10.3390/ijms22041994

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