title: Pigment epithelium-derived factor enhances tumor response to radiation through vasculature normalization in allografted lung cancer in mice.
abstract: This study aimed to explore the potential therapeutic effects of the combination of pigment epithelium-derived factor (PEDF) and radiation on lung cancer. The Lewis lung cancer (LLC) allografts in nude mice were treated with radiation, PEDF and PEDF combined with radiation. The morphologic changes of tumor vasculature and the hypoxic fraction of tumor tissues were evaluated. Significant inhibition of tumor growth was observed when radiation was applied between the 3rd and 7th day (the vasculature normalization window) after the initiation of PEDF treatment. During the vasculature normalization window, the tumor blood vessels in PEDF-treated mice were less tortuous and more uniform than those in the LLC allograft tumor treated with phosphate-buffered saline. Meanwhile, the thickness of the basement membrane was remarkably reduced and pericyte coverage was significantly increased with the PEDF treatment. We also found that tumor hypoxic fraction decreased during the 3rd to the 7th day after PEDF treatment, suggesting improved intratumoral oxygenation. Taken together, our results show that PEDF improved the effects of radiation therapy on LLC allografts by inducing a vascular normalization window from the 3rd to the 7th day after PEDF treatment. Our findings provide a basis for treating lung cancer with the combination of PEDF and radiation.
authors.affiliation: 1] Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Province, Guangzhou, China [2] Cancer Center, Affiliated Hospital of Guangdong Medical College, Guangdong Province, Zhanjiang, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Cancer Center, 3rd People's Hospital, Guangdong Province, Dongguan City, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Province, Guangzhou, China.
authors.forename: F
authors.initials: F
authors.lastname: Peng
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical College, Guangdong Province, Zhanjiang, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Yu
authors.affiliation: Cancer Center, Affiliated Hospital of Guangdong Medical College, Guangdong Province, Zhanjiang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zuo
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong Province, Guangzhou, China.
authors.forename: Z
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Zhejiang Cancer Hospital, Zhejiang Province, Hangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Zhejiang Cancer Hospital, Zhejiang Province, Hangzhou, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Province, Guangzhou, China.
authors.forename: X
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Province, Guangzhou, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Zhejiang Cancer Hospital, Zhejiang Province, Hangzhou, China.
authors.forename: H
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Province, Guangzhou, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangdong Province, Guangzhou, China.
authors.forename: G
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of Radiation Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Province, Guangzhou, China.
authors.forename: M
authors.initials: M
authors.lastname: Chen
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000187:drug effects / Q000473:pathology; D002196:Capillaries / Q000187:drug effects / Q000473:pathology; D018827:Carcinoma, Lewis Lung / Q000098:blood supply / Q000473:pathology / Q000628:therapy*; D015687:Cell Hypoxia; D059248:Chemoradiotherapy; D005136:Eye Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D009414:Nerve Growth Factors / Q000494:pharmacology / Q000627:therapeutic use*; D020286:Pericytes / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015843:Serpins / Q000494:pharmacology / Q000627:therapeutic use*; D047368:Tumor Burden; D023041:Xenograft Model Antitumor Assays; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D009414:Nerve Growth Factors; D011838:Radiation-Sensitizing Agents; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor