title: Messenger RNA expression of COX-2 and angiogenic factors in primary colorectal cancer and corresponding liver metastasis.
abstract: Several new drugs that are targeted towards various angiogenic factors have shown considerable potential for controlling tumor proliferation and metastases. Expression levels of the targeted genes in primary tumors and metastases should be understood to maximize the use of such drugs. The present study aimed to clarify associations between mRNA levels of cyclooxygenase 2 (COX-2) and angiogenic factors [vascular endothelial growth factor (VEGF) and interleukin-8 (IL-8)] in primary colorectal cancer and in corresponding liver metastasis. We also compared these gene expressions of primary colorectal cancer between patients with and without liver metastasis. In 31 pairs of formalin-fixed and paraffin-embedded primary and metastatic liver tumors as well as 27 specimens of consecutive stage II patients without recurrence, mRNA was quantified by real-time reverse transcription-polymerase chain reaction following the laser capture microdissection. We found a significantly positive correlation in IL-8 between primary tumors and matched liver metastases (p=0.034, rs=0.39) and in VEGF (p=0.0083, rs=0.48), but not in COX-2, which was associated with both VEGF (p=0.044, rs=0.37) and IL-8 (p=0.0004, rs=0.64) in primary colorectal cancers. Multiple regression analysis revealed that COX-2 was independently associated with IL-8 (p<0.0001). There were no differences in mRNA levels between patients with and without liver metastasis. The mRNA levels of VEGF and IL-8 in liver metastasis can be predicted from those in primary colorectal cancer. COX-2 might exert angiogenic activity more through the IL-8, than the VEGF pathway. These angiogenic factors were sufficiently up-regulated before hematogenous metastasis. These preliminary data merit further validation studies.
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan. h-kobayashi.srg2@tmd.ac.jp
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Kobayashi
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Uetake
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Higuchi
authors.forename: Masamichi
authors.initials: M
authors.lastname: Yasuno
authors.forename: Masayuki
authors.initials: M
authors.lastname: Enomoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Iida
authors.forename: Heinz-Josef
authors.initials: HJ
authors.lastname: Lenz
authors.forename: Kathleen D
authors.initials: KD
authors.lastname: Danenberg
authors.forename: Peter V
authors.initials: PV
authors.lastname: Danenberg
mesh_terms: D000368:Aged; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000502:physiology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D051546:Cyclooxygenase 2