Expression of angiopoietin 1, 2 and their common receptor Tie2 in human gastric carcinoma: implication for angiogenesis.
Angiogenesis, formation of new microvessels providing oxygen and nutrient supply, is essential for tumor growth. It is dependent on the production of angiogenic growth factors by tumor cells. Angiopoietin 1 (Ang-1) and 2 (Ang-2) and their common receptor, Tie2, are thought to be critical regulators of tumor angiogenesis. We examined expression of Ang-1, Ang-2, and their common receptor Tie2 mRNAs and proteins in gastric cancers using in situ hybridization and immunohistochemistry. We also investigated the relationship between their expression and differentiation of cancer cells, lymph node metastasis, tumor size, depth of cancer cell invasion, TNM staging and microvessel density (MVD). The expression of Ang-1, Ang-2, and Tie2 mRNA in cancer cells significantly correlated with the MVD (p<0.001, <0.001 and =0.019, respectively). Ang-1 and Tie2 positivity correlated with advanced gastric cancers (p<0.05) and larger cancers had higher positive rates of Ang-1, Ang-2, and Tie2 mRNA expression (p<0.001, =0.010 and =0.039, respectively). Significant positive correlations were also found between mRNA expression of Tie2 and those of Ang-1 and Ang-2 (p<0.01 and <0.001, respectively). These findings indicate that the expression of Ang-1 and Ang-2 is important for tumor angiogenesis, and suggest a possible role of autocrine/paracrine function of angiopoietin/Tie2 system in gastric cancer progression.
Moon
Woo Sung
WS
Department of Pathology, Chonbuk National University, Medical School, Institute for Medical Sciences and Center for Healthcare Technology Development, Dukjin-gu, Jeonju, Korea. mws@chonbuk.ac.kr
Park
Ho Sung
HS
Yu
Ki Hoon
KH
Jang
Kyu Yun
KY
Kang
Myoung Jae
MJ
Park
Harry
H
Tarnawski
Andrzej S
AS
D000230:Adenocarcinoma / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D042683:Angiopoietin-1 / Q000235:genetics* / Q000378:metabolism*; D042702:Angiopoietin-2 / Q000235:genetics* / Q000378:metabolism*; D018279:Carcinoma, Signet Ring Cell / Q000098:blood supply / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D042787:Receptor, TIE-2 / Q000235:genetics* / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000098:blood supply / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
C467630:ANGPT1 protein, human; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D042787:Receptor, TIE-2