The chemokine receptor CXCR7 is a critical regulator for the tumorigenesis and development of papillary thyroid carcinoma by inducing angiogenesis in vitro and in vivo

Tumour Biol. 2016 Feb;37(2):2415-23. doi: 10.1007/s13277-015-4051-5. Epub 2015 Sep 17.

Abstract

Papillary thyroid carcinoma (PTC) is a well-differentiated neoplasm, but it can transfer early to cervical lymph nodes. Accumulating evidences have confirmed the important roles of CXCR7 in tumor cell proliferation, invasion, metastasis, and angiogenesis. Our previous study demonstrated CXCR7 modulated proliferation, apoptosis, and invasion of PTC cells. In this study, we evaluated the effect of expression of CXCR7 in PTC cells on angiogenesis and whether its expression had an influence on the tumor growth of PTC in vivo. We evaluated the effect of CXCR7 on interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF) secretion, angiogenesis, and tumor growth by ELISA, endothelial tube formation assay, and a xenograft tumor model in nude mice. Immunohistochemistry was used to assess expression of CD34 in tumor of mice. In vitro and in vivo studies in PTC cells suggested that the alteration of CXCR7 expression was correlated with angiogenesis and tumor growth. Moreover, CXCR7 mediated the expression of IL-8 and VEGF, which might be involved in the regulation of tumor angiogenesis. These findings suggest that CXCR7 affects the growth of PTC cells and participates in the tumorigenesis of PTC, probably through regulating angiogenesis by the proangiogenic VEGF or IL-8.

Keywords: Angiogenesis; CXCR7; Chemokine receptor; Interleukin-8; Thyroid neoplasms; Vascular endothelial growth factor.

MeSH terms

  • Angiogenesis Inducing Agents / metabolism
  • Animals
  • Antigens, CD34 / metabolism
  • Apoptosis / physiology
  • Carcinogenesis / metabolism*
  • Carcinogenesis / pathology*
  • Carcinoma / metabolism*
  • Carcinoma / pathology*
  • Carcinoma, Papillary
  • Cell Line, Tumor
  • Cell Movement / physiology
  • Cell Proliferation / physiology
  • Female
  • Humans
  • Interleukin-8 / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neovascularization, Pathologic / metabolism*
  • Neovascularization, Pathologic / pathology
  • Receptors, CXCR / metabolism*
  • Signal Transduction / physiology
  • Thyroid Cancer, Papillary
  • Thyroid Neoplasms / metabolism*
  • Thyroid Neoplasms / pathology*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • ACKR3 protein, human
  • Angiogenesis Inducing Agents
  • Antigens, CD34
  • Interleukin-8
  • Receptors, CXCR
  • Vascular Endothelial Growth Factor A