We examined the autocrine/paracrine role of interleukin-8 (CXCL8) and the functional significance of CXCL8 receptors, CXCR1 and CXCR2, in human malignant melanoma proliferation, migration, invasion and angiogenesis. We found that a panel of seven cell lines, even though at different extent, secreted CXCL8 protein, and expressed CXCR1 and CXCR2 independently from the CXCL8 expression, but depending on the oxygen level. In fact, hypoxic exposure increases the expression of CXCR1 and CXCR2. The cell proliferation of both M20 and A375SM lines, expressing similar levels of both CXCR1 and CXCR2 but secreting low and high amounts of CXCL8, respectively, was significantly enhanced by CXCL8 exposure and reduced by CXCL8, CXCR1 and CXCR2 neutralising antibodies, indicating the autocrine/paracrine role of CXCL8 in melanoma cell proliferation. Moreover, an increased invasion and migration in response to CXCL8 was observed in several cell lines, and a further enhancement evidenced under hypoxic conditions. A CXCL8-dependent in vivo vessel formation, evaluated through a matrigel assay, was also demonstrated. Furthermore, when neutralising antibodies against CXCR1 or CXCR2 were used, only the involvement of CXCR2, but not CXCR1 was observed on cell migration and invasion, while both receptors played a role in angiogenesis. In summary, our data demonstrate that CXCL8 induces cell proliferation and angiogenesis through both receptors and that CXCR2 plays an important role in regulating the CXCL8-mediated invasive and migratory behaviour of human melanoma cells. Thus, blocking the CXCL8 signalling axis promises an improvement for the therapy of cancer and, in particular, of metastatic melanoma. (C) 2009 Elsevier Ltd. All rights reserved.

Gabellini, C., Trisciuoglio, D., Desideri, M., Candiloro, A., Ragazzoni, Y., Orlandi, A., et al. (2009). Functional activity of CXCL8 receptors, CXCR1 and CXCR2, on human malignant melanoma progression. EUROPEAN JOURNAL OF CANCER, 45(14), 2618-2627 [10.1016/j.ejca.2009.07.007].

Functional activity of CXCL8 receptors, CXCR1 and CXCR2, on human malignant melanoma progression

ORLANDI, AUGUSTO;
2009-01-01

Abstract

We examined the autocrine/paracrine role of interleukin-8 (CXCL8) and the functional significance of CXCL8 receptors, CXCR1 and CXCR2, in human malignant melanoma proliferation, migration, invasion and angiogenesis. We found that a panel of seven cell lines, even though at different extent, secreted CXCL8 protein, and expressed CXCR1 and CXCR2 independently from the CXCL8 expression, but depending on the oxygen level. In fact, hypoxic exposure increases the expression of CXCR1 and CXCR2. The cell proliferation of both M20 and A375SM lines, expressing similar levels of both CXCR1 and CXCR2 but secreting low and high amounts of CXCL8, respectively, was significantly enhanced by CXCL8 exposure and reduced by CXCL8, CXCR1 and CXCR2 neutralising antibodies, indicating the autocrine/paracrine role of CXCL8 in melanoma cell proliferation. Moreover, an increased invasion and migration in response to CXCL8 was observed in several cell lines, and a further enhancement evidenced under hypoxic conditions. A CXCL8-dependent in vivo vessel formation, evaluated through a matrigel assay, was also demonstrated. Furthermore, when neutralising antibodies against CXCR1 or CXCR2 were used, only the involvement of CXCR2, but not CXCR1 was observed on cell migration and invasion, while both receptors played a role in angiogenesis. In summary, our data demonstrate that CXCL8 induces cell proliferation and angiogenesis through both receptors and that CXCR2 plays an important role in regulating the CXCL8-mediated invasive and migratory behaviour of human melanoma cells. Thus, blocking the CXCL8 signalling axis promises an improvement for the therapy of cancer and, in particular, of metastatic melanoma. (C) 2009 Elsevier Ltd. All rights reserved.
2009
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/08 - ANATOMIA PATOLOGICA
English
Con Impact Factor ISI
Cell hypoxia; Cell proliferation; Chemotaxis; CXCR1; CXCR2; Interleukin-8; Melanoma; Neoplasm invasiveness; Pathologic neovascularisation
Gabellini, C., Trisciuoglio, D., Desideri, M., Candiloro, A., Ragazzoni, Y., Orlandi, A., et al. (2009). Functional activity of CXCL8 receptors, CXCR1 and CXCR2, on human malignant melanoma progression. EUROPEAN JOURNAL OF CANCER, 45(14), 2618-2627 [10.1016/j.ejca.2009.07.007].
Gabellini, C; Trisciuoglio, D; Desideri, M; Candiloro, A; Ragazzoni, Y; Orlandi, A; Zupi, G; Del Bufalo, D
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/39149
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