title: Biologic effects of platelet-derived growth factor receptor α blockade in uterine cancer.
abstract: OBJECTIVE
  Platelet-derived growth factor receptor α (PDGFRα) expression is frequently observed in many kinds of cancer and is a candidate for therapeutic targeting. This preclinical study evaluated the biologic significance of PDGFRα and PDGFRα blockade (using a fully humanized monoclonal antibody, 3G3) in uterine cancer.
  
  
  METHODS
  Expression of PDGFRα was examined in uterine cancer clinical samples and cell lines, and biologic effects of PDGFRα inhibition were evaluated using in vitro (cell viability, apoptosis, and invasion) and in vivo (orthotopic) models of uterine cancer.
  
  
  RESULTS
  PDGFRα was highly expressed and activated in uterine cancer samples and cell lines. Treatment with 3G3 resulted in substantial inhibition of PDGFRα phosphorylation and of downstream signaling molecules AKT and mitogen-activated protein kinase (MAPK). Cell viability and invasive potential of uterine cancer cells were also inhibited by 3G3 treatment. In orthotopic mouse models of uterine cancer, 3G3 monotherapy had significant antitumor effects in the PDGFRα-positive models (Hec-1A, Ishikawa, Spec-2) but not in the PDGFRα-negative model (OVCA432). Greater therapeutic effects were observed for 3G3 in combination with chemotherapy than for either drug alone in the PDGFRα-positive models. The antitumor effects of therapy were related to increased apoptosis and decreased proliferation and angiogenesis.
  
  
  CONCLUSIONS
  These findings identify PDGFRα as an attractive target for therapeutic development in uterine cancer.
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandAuthors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Ju-Won
authors.initials: JW
authors.lastname: Roh
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: XiaoYun
authors.initials: X
authors.lastname: Yang
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Nicholas B
authors.initials: NB
authors.lastname: Jennings
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Vasudha
authors.initials: V
authors.lastname: Sehgal
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Bo Hwa
authors.initials: BH
authors.lastname: Sohn
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Hee Dong
authors.initials: HD
authors.lastname: Han
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandAuthors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Sun Joo
authors.initials: SJ
authors.lastname: Lee
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandAuthors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Duangmani
authors.initials: D
authors.lastname: Thanapprapasr
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Justin
authors.initials: J
authors.lastname: Bottsford-Miller
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Behrouz
authors.initials: B
authors.lastname: Zand
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Dalton
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Previs
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Ashley N
authors.initials: AN
authors.lastname: Davis
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandAuthors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Koji
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Ju-Seog
authors.initials: JS
authors.lastname: Lee
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Prahlad
authors.initials: P
authors.lastname: Ram
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
authors.affiliation: Authors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandAuthors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, ThailandAuthors' Affiliations: Departments of Gynecologic Oncology and Reproductive Medicine and Cancer Biology, Center for RNA Interference and Non-Coding RNA, the University of Texas MD Anderson Cancer Center, Houston, Texas; University of Southern California, Los Angeles, California; Department of Obstetrics and Gynecology, Dongguk University; Departments of Systems Biology and Obstetrics and Gynecology, Konkuk University, Seoul, Korea; and Department of Obstetrics and Gynecology, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand asood@mdanderson.org.
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004357:Drug Synergism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D020796:Receptor, Platelet-Derived Growth Factor alpha; D051057:Proto-Oncogene Proteins c-akt; D020928:Mitogen-Activated Protein Kinases