The relationship between platelet-derived growth
factor expression and angiogenesis/lymphangiogenesis in cervical cancer
The relationship between platelet-derived growth
factor expression and angiogenesis/lymphangiogenesis in cervical cancer
Guocheng LIU MD1,Shouhua YANG MD2,Zehua WANG MD2,
1.Department of Obstetrics
and Gynecology, Maternal and Child Health Hospital of Guangdong Province,
Guangzhou 510010, China; 2.Department of Obstetrics
and Gynecology, Union Hospital, Tongji Medical College, Huazhong University
of Science and Technology, Wuhan 430022, China;
Abstract：This paper is aimed to examine if changes in platelet-derived growth factor (PDGF) expression at different stages of cervical cancer are related to the variation in blood vessel density (BVD) and lymphatic vessel density (LVD) to evaluate the relationship between PDGF expression and stages and metastasis of cervical cancer. Polymerase chain reaction (PCR) and RT-PCR were used to detect the expression levels of PDGF in 45 cervical cancer tissue samples (the experimental group). The samples were immunohistochemically stained with monoclonal antibodies D2-40 and CD34, and BVD and LVD were measured. The expressions of PDGF-A, -B, and- D were all higher in the experimental group than in the control group (P<0.05); no significant difference was found in the expression of PDGF-C between the experimental group and the control group (P>0.05). PDGF-A and -B expression was positively related with BVD and LVD (P<0.01, R= 0.49, 0.527, 0.327, 0.68). The expression levels of PDGF-C and -D were not significantly related with BVD and LVD. At the early stage of cervical cancer, BVD and LVD were significantly higher than in the controls (P<0.01). The BVD and LVD in tissues in the surrounding areas of cervical cancer were significantly higher than in tissues at cancer center, and LVD was related to lymph node metastasis (P<0.001). BVD and LVD were not associated with the differentiation and pathological stages of cervical cancer. The expressions of PDGF-A, -B, and -D in cervical cancer were closely related with the clinical stages of cervical cancer. PDGF-A and -B were intimately associated with the lymph node metastasis and prognosis of cervical cancer.
. The relationship between platelet-derived growth
factor expression and angiogenesis/lymphangiogenesis in cervical cancer[J]. Front. Med., 2009, 3(4): 447-451.
Guocheng LIU MD, Shouhua YANG MD, Zehua WANG MD, . The relationship between platelet-derived growth
factor expression and angiogenesis/lymphangiogenesis in cervical cancer. Front. Med., 2009, 3(4): 447-451.
Beasley N J, Prevo R, Banerji S, Leek R D, Moore J, van Trappen P, Cox G, Harris A L, Jackson D G. Intratumoral lymphangiogenesis and lymph node metastasis in headand neck cancer. Cancer Res, 2002, 62(5): 1315–1320
Rakowicz-Szulczynska E M, McIntosh D G, Perry M, Smith M L. PDGF AA asmediator in nicotine-dependent carcinogenesis. Carcinogenesis, 1996, 17(9): 1813–1818 doi: 10.1093/carcin/17.9.1813
Taja-Chayeb L, Chavez-Blanco A, Martínez-Tlahuel J, González-Fierro A, Candelaria M, Chanona-Vilchis J, Robles E, Dueñas-Gonzalez A. Expression of platelet derivedgrowth factor family members and the potential role of imatinib mesylatefor cervical cancer. Cancer Cell Int, 2006, 60: 22 doi: 10.1186/1475-2867-6-22
Cao R, Björndahl MA, Religa P, Clasper S, Garvin S, Galter D, Meister B, Ikomi F, Tritsaris K, Dissing S, Ohhashi T, Jackson D G, Cao Y. PDGF-BB inducesintratumoral lymphangiogenesis and promotes lymphatic metastasis. Cancer Cell, 2004, 6(4): 333–345 doi: 10.1016/j.ccr.2004.08.034
Cao R, Bråkenhielm E, Li X, Pietras K, Widenfalk J, Ostman A, Eriksson U, Cao Y. Angiogenesis stimulated byPDGF-CC, a novel member in the PDGF family, involves activation ofPDGFR-alphaalpha and-alphabeta receptors. FASEB J, 2002, 16(12): 1575–1583 doi: 10.1096/fj.02-0319com
Marra F, Gentilini A, Pinzani M, Choudhury G G, Parola M, Herbst H, Dianzani M U, Laffi G, Abboud H E, Gentilini P.Phosphatidylinositol-3 kinase is requiredfor platelet-derived growth factor's actions on hepatic stellate cells. Gastroenterology, 1997, 112(4): 1406–1409 doi: 10.1016/S0016-5085(97)70144-6
Shikada Y, Yonemitsu Y, Koga T, Onimaru M, Nakano T, Okano S, Sata S, Nakagawa K, Yoshino I, Maehara Y, Sueishi K. Platelet-derived growth factor-AA is an essential andautocrineregulator of vascular endothelial growth factorexpressionin non-small cell lung carcinomas. CancerResearch, 2005, 65(16): 7241–7248 doi: 10.1158/0008-5472.CAN-04-4171
Zhang T, Sun H C, Xu Y, Zhang K Z, Wang L, Qin L X, Wu W Z, Liu Y K, Ye S L, Tang Z Y. Overexpression ofplatelet-derived growthfactor receptor alpha inendothelial cells of hepatocellular carcinomaassociatedwith high metastatic potential. Clin Cancer Res, 2005, 11(24 Pt 1): 8557–8563 doi: 10.1158/1078-0432.CCR-05-0944
Bergsten E, Uutela M, Li X, Pietras K, Ostman A, Heldin C H, Alitalo K, Eriksson U. PDGF-D is a specific, protease-activatedligand for the PDGF beta- receptor. NatCell Biol, 2001, 3(5): 512–516 doi: 10.1038/35074588
Fredriksson L, Li H, Eriksson U. The PDGF family: four gene products form five dimericisoforms. Cytokine Growth Factor Rev, 2004, 15(4): 197–204 doi: 10.1016/j.cytogfr.2004.03.007
Zhang J, Cao R, Zhang Y, Jia T, Cao Y, Wahlberg E. Differentialroles of PDGFR-alpha and PDGFR-beta in angiogenesis and vessel stability. FASEB J, 2009, 23(1): 153–163 doi: 10.1096/fj.08-113860
Gao P, Zhou G Y, Yin G, Liu Y, Liu Z Y, Zhang J, Hao C Y. Lymphatic vessel densityas a prognostic indicator for patients with stage I cervical carcinoma. Hum Pathol, 2006, 37(6): 719–725 doi: 10.1016/j.humpath.2006.01.025
He Y, Rajantie I, Ilmonen M, Makinen T, Karkkainen M J, Haiko P, Salven P, Alitalo K. Preexisting lymphatic endotheliumbut not endothelial progenitor cells are essential for tumor lymphangiogenesisand lymphatic metastasis. Cancer Res, 2004, 64(11): 3737–3740 doi: 10.1158/0008-5472.CAN-04-0088
