+ Site Statistics
References:
54,258,434
Abstracts:
29,560,870
PMIDs:
28,072,757
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Radiation-induced thymidine phosphorylase upregulation in rectal cancer is mediated by tumor-associated macrophages by monocyte chemoattractant protein-1 from cancer cells



Radiation-induced thymidine phosphorylase upregulation in rectal cancer is mediated by tumor-associated macrophages by monocyte chemoattractant protein-1 from cancer cells



International Journal of Radiation Oncology, Biology, Physics 73(3): 853-860



The mechanisms of thymidine phosphorylase (TP) regulation induced by radiation therapy (XRT) in various tumors are poorly understood. We investigated the effect and mechanisms of preoperative XRT on TP expression in rectal cancer tissues. TP expression and CD68 and monocyte chemoattractant protein-1 (MCP-1) levels in rectal cancer tissues and cancer cell lines were evaluated before and after XRT in Western blotting, immunohistochemistry, enzyme-linked immunoassay, and reverse transcription-polymerase chain reaction studies. Isolated peripheral blood monocytes were used in the study of chemotaxis under the influence of MCP-1 released by irradiated colon cancer cells. Expression of TP was significantly elevated by 9 Gy of XRT in most rectal cancer tissues but not by higher doses of XRT. In keeping with the close correlation of the increase in both TP expression and the number of tumor-associated macrophages (TAMs), anti-TP immunoreactivity was found in the CD68-positive TAMs and not the neoplastic cells. Expression of MCP-1 was increased in most cases after XRT, and this increase was strongly correlated with TP expression. However, this increase in MCP-1 expression occurred in tumor cells and not stromal cells. The XRT upregulated MCP-1 mRNA and also triggered the release of MCP-1 protein from cultured colon cancer cells. The supernatant of irradiated colon cancer cells showed strong chemotactic activity for monocyte migration, but this activity was completely abolished by neutralizing antibody. Use of XRT induces MCP-1 expression in cancer cells, which causes circulating monocytes to be recruited into TAMs, which then upregulate TP expression in rectal cancer tissues.

(PDF emailed within 0-6 h: $19.90)

Accession: 055345388

Download citation: RISBibTeXText

PMID: 19215821

DOI: 10.1016/j.ijrobp.2008.07.068


Related references

Upregulation of thymidine phosphorylase in rectal cancer tissues by mitomycin C. Journal of Surgical Oncology 93(1): 47-55, 2005

Antisense to LOX-1 inhibits oxidized LDL-mediated upregulation of monocyte chemoattractant protein-1 and monocyte adhesion to human coronary artery endothelial cells. Circulation 101(25): 2889-2895, 2000

Thymidine phosphorylase-mediated angiogenesis regulated by thymidine phosphorylase inhibitor in human ovarian cancer cells in vivo. International Journal of Oncology 22(5): 961-967, 2003

Nifedipine inhibits tumor necrosis factor-alpha-induced upregulation of monocyte chemoattractant protein-1 mRNA levels by suppressing CD40 expression in endothelial cells. Drugs Under Experimental and Clinical Research 31(1): 13-17, 2005

Differences and relationships of thymidine phosphorylase expression in tumor-associated macrophages and cancer cells in squamous cell carcinoma of the esophagus. Diseases of the Esophagus 15(1): 67-73, 2002

Upregulation of thymidine phosphorylase (TP) by radiation (XRT): Phase II study of capecitabine (CAP) with XRT in pts with locally advanced (LA) pancreatic cancer. Journal of Clinical Oncology 24(18_suppl): 14001-14001, 2016

Anthracyclines and taxanes induce the upregulation of thymidine phosphorylase in breast cancer cells. Anti-Cancer Drugs 18(8): 883-888, 2007

Upregulation of the proinflammatory cytokine-induced neutrophil chemoattractant-1 and monocyte chemoattractant protein-1 in rats' intestinal anastomotic wound healing--does it matter?. Asian Journal of Surgery 37(2): 86-92, 2015

Mechanical stretch induces monocyte chemoattractant activity via an NF-kappaB-dependent monocyte chemoattractant protein-1-mediated pathway in human mesangial cells: inhibition by rosiglitazone. Journal of the American Society of Nephrology 16(3): 688-696, 2005

TGF-beta induces expression of monocyte chemoattractant JE/monocyte chemoattractant protein 1 via transcriptional factor AP-1 induced by protein kinase in osteoblastic cells. Journal of Immunology 155(1): 419-426, 1995

Monocyte chemoattractant protein-1 blockade inhibits lung cancer tumor growth by altering macrophage phenotype and activating CD8+ cells. American Journal of Respiratory Cell and Molecular Biology 44(2): 230-237, 2011

TGF-b induces expression of monocyte chemoattractant JE/monocyte chemoattractant protein 1 via transcriptional factor AP-1 induced by protein kinase in osteoblastic cells. Journal of Immunology 155: 9-26, 1995

Activation of thromboxane A2 receptor (TP) increases the expression of monocyte chemoattractant protein -1 (MCP-1)/chemokine (C-C motif) ligand 2 (CCL2) and recruits macrophages to promote invasion of lung cancer cells. Plos One 8(1): E54073-E54073, 2013

Thymidine phosphorylase expression in tumor-infiltrating macrophages may be correlated with poor prognosis in uterine endometrial cancer. Human Pathology 33(11): 1105-1113, 2002

Monocyte chemoattractant protein 1 and CD40 ligation have a synergistic effect on vascular endothelial growth factor production through cyclooxygenase 2 upregulation in gastric cancer. Journal of Gastroenterology 43(3): 216-224, 2008