Remodeling of the tumor microenvironment by combined treatment with a novel radiosensitizer, {alpha}-sulfoquinovosylmonoacylglycerol ({alpha}-SQMG) and X-irradiation.
OBJECTIVE
The purpose of this study was to examine the effects of combined treatment with a specific type of sulfoglycolipid, α-sulfoquinovosylmonoacylglycerol (α-SQMG), and X-irradiation (XRT) on the remodeling of tumor microenvironments.


METHODS
A human colon cancer cell line, SW480, was used in this study. The cells were injected subcutaneously into nude mice and the resulting tumors were treated with α-SQMG that was injected intravenously and/or X-irradiation (XRT). The tumor volumes were monitored and the microenvironments of the treated tumors were immunohistochemically analyzed for angiogenesis, pericyte recruitment, and hypoxic fractions using markers for CD31, collagen IV, α-Sma, and pimonidazole.


RESULTS
The combined treatment with α-SQMG (five daily injections from days zero to four) and X-irradiation (two fractions on days zero and three) synergistically enhanced the radioresponse of tumor growth in vivo, whereas α-SQMG treatment alone had no effect. The tumor vessel density was significantly decreased at days 10 and 20 after initiating the combined treatment. On day 20, areas with overlapping CD31 and collagen IV expression were rarely observed, suggesting that the normal structures of most tumor vessels had collapsed. α-Sma staining was significantly increased and pimonidazole staining was significantly reduced at 24 and 72 h, but not 6 h, after the first combined treatment.


CONCLUSIONS
The combined treatment induced remodeling of the microenvironments in SW480 tumors, which might contribute to the radiosensitization to the second irradiation.
Oral Radiation Oncology, Department of Oral Restitution, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Keisuke
K
Ohta
Hiroshi
H
Murata
Yoko
Y
Mori
Masahiro
M
Ishima
Fumio
F
Sugawara
Kengo
K
Sakaguchi
Masahiko
M
Miura
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D003131:Combined Modality Therapy; D006017:Glycolipids / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000188:drug therapy / Q000532:radiotherapy; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment / Q000187:drug effects* / Q000528:radiation effects*; D014964:X-Ray Therapy; D023041:Xenograft Model Antitumor Assays
C477365:1-mono-O-acyl-3-O-(alpha-D-sulfoquinovosyl)-glyceride; D006017:Glycolipids; D011838:Radiation-Sensitizing Agents