Impact of KITENIN on tumor angiogenesis and lymphangiogenesis in colorectal cancer.
Angiogenesis and lymphangiogenesis are involved in the dissemination of tumor cells from solid tumors to regional lymph nodes and various distant sites. KAI1 COOH-terminal interacting tetraspanin (KITENIN) contributes to tumor progression and poor clinical outcomes in various cancers including colorectal cancer. The aim of the present study was to evaluate whether KITENIN affects tumor angiogenesis and lymphangiogenesis in colorectal cancer. A KITENIN small interfering RNA vector was used to silence KITENIN expression in colorectal cancer cell lines including DLD1 and SW480 cells. To evaluate the ability of KITENIN to induce angiogenesis and lymphangiogenesis in human umbilical vein endothelial cells (HUVECs) and lymphatic endothelial cells (HLECs), we performed Matrigel invasion and tube formation assays. Immunohistochemistry was used to determine the expression of KITENIN in colorectal cancer tissues. Angiogenesis and lymphangiogenesis were evaluated by immunostaining with CD34 and D2-40 antibodies. KITENIN silencing inhibited both HUVEC invasion and tube formation in the DLD1 and SW480 cells. KITENIN silencing led to decreased expression of the angiogenic inducers vascular endothelial growth factor (VEGF)-A and hypoxia-inducible factor-1α and increased expression of the angiogenic inhibitor angiostatin. KITENIN silencing did not inhibit either HLEC invasion or tube formation in all tested cells, but it resulted in decreased expression of the lymphangiogenic inducer VEGF-C. KITENIN expression was significantly associated with tumor stage, depth of invasion, lymph node and distant metastases and poor survival. The mean microvessel density was significantly higher in the KITENIN-positive tumors than that in the KITENIN-negative tumors. However, the mean lymphatic vessel density of KITENIN-positive tumors was not significantly higher than that of the KITENIN-negative tumors. These results suggest that KITENIN promotes tumor progression by enhancing angiogenesis in colorectal cancer.
Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
Hyung-Hoon
HH
Oh
Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
Kang-Jin
KJ
Park
Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
Nuri
N
Kim
Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
Sun-Young
SY
Park
Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
Young-Lan
YL
Park
Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
Chan-Young
CY
Oak
Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
Dae-Seong
DS
Myung
Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
Sung-Bum
SB
Cho
Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
Wan-Sik
WS
Lee
Department of Pharmacology, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
Kyung-Keun
KK
Kim
Department of Internal Medicine, Chonnam National University Medical School, Dong-ku, Gwangju 501-757, Republic of Korea.
Young-Eun
YE
Joo
D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D042583:Lymphangiogenesis; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D016019:Survival Analysis; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism
D002352:Carrier Proteins; D008565:Membrane Proteins; D034741:RNA, Small Interfering; C488287:VANGL1 protein, human; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C