PMID- 19215821
OWN - NLM
STAT- MEDLINE
DCOM- 20090303
LR  - 20090213
IS  - 1879-355X (Electronic)
IS  - 0360-3016 (Linking)
VI  - 73
IP  - 3
DP  - 2009 Mar 1
TI  - Radiation-induced thymidine phosphorylase upregulation in rectal cancer is 
      mediated by tumor-associated macrophages by monocyte chemoattractant protein-1 
      from cancer cells.
PG  - 853-60
LID - 10.1016/j.ijrobp.2008.07.068 [doi]
AB  - PURPOSE: 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. METHODS AND MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.
FAU - Kim, Tae-Dong
AU  - Kim TD
AD  - Department of Biochemistry, Chungnam National University College of Medicine, 
      Daejon, Korea.
FAU - Li, Ge
AU  - Li G
FAU - Song, Kyoung-Sub
AU  - Song KS
FAU - Kim, Jin-Man
AU  - Kim JM
FAU - Kim, Jun-Sang
AU  - Kim JS
FAU - Kim, Jong-Seok
AU  - Kim JS
FAU - Yun, Eun-Jin
AU  - Yun EJ
FAU - Park, Jong-Il
AU  - Park JI
FAU - Park, Hae-Duck
AU  - Park HD
FAU - Hwang, Byung-Doo
AU  - Hwang BD
FAU - Lim, Kyu
AU  - Lim K
FAU - Yoon, Wan-Hee
AU  - Yoon WH
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Int J Radiat Oncol Biol Phys
JT  - International journal of radiation oncology, biology, physics
JID - 7603616
RN  - 0 (Antigens, CD)
RN  - 0 (Antigens, Differentiation, Myelomonocytic)
RN  - 0 (CD68 antigen, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - EC 2.4.2.4 (Thymidine Phosphorylase)
SB  - IM
MH  - Antigens, CD/*metabolism
MH  - Antigens, Differentiation, Myelomonocytic/*metabolism
MH  - Cell Line, Tumor/enzymology/radiation effects
MH  - Cell Migration Assays, Leukocyte/methods
MH  - Cell Migration Assays, Macrophage
MH  - Chemokine CCL2/*metabolism
MH  - Colonic Neoplasms/metabolism/pathology
MH  - HT29 Cells/enzymology/radiation effects
MH  - Humans
MH  - Macrophages/physiology
MH  - Monocytes/*physiology
MH  - RNA, Messenger/metabolism
MH  - Radiotherapy Dosage
MH  - Rectal Neoplasms/*metabolism/radiotherapy
MH  - Thymidine Phosphorylase/*metabolism
MH  - U937 Cells/enzymology/radiation effects
MH  - Up-Regulation/physiology/*radiation effects
EDAT- 2009/02/14 09:00
MHDA- 2009/03/04 09:00
CRDT- 2009/02/14 09:00
PHST- 2008/05/18 00:00 [received]
PHST- 2008/07/22 00:00 [revised]
PHST- 2008/07/22 00:00 [accepted]
PHST- 2009/02/14 09:00 [entrez]
PHST- 2009/02/14 09:00 [pubmed]
PHST- 2009/03/04 09:00 [medline]
AID - S0360-3016(08)03599-2 [pii]
AID - 10.1016/j.ijrobp.2008.07.068 [doi]
PST - ppublish
SO  - Int J Radiat Oncol Biol Phys. 2009 Mar 1;73(3):853-60. doi: 
      10.1016/j.ijrobp.2008.07.068.