Top

Published in:

01-05-2009 | ORIGINAL ARTICLE

The Simultaneous Expression of Peroxisome Proliferator-Activated Receptor Delta and Cyclooxygenase-2 May Enhance Angiogenesis and Tumor Venous Invasion in Tissues of Colorectal Cancers

Authors: Masahiro Yoshinaga, Yosuke Kitamura, Tomohito Chaen, Shinsaku Yamashita, Satoru Tsuruta, Teruaki Hisano, Yoichi Ikeda, Hironori Sakai, Kazuhiko Nakamura, Ryoichi Takayanagi, Yoichi Muto

Published in: Digestive Diseases and Sciences | Issue 5/2009

Abstract

We conducted this study to evaluate the impact of the expression of peroxisome proliferator-activated receptor delta on angiogenesis in tissue samples of colorectal cancer. We examined 52 samples of primary human colorectal carcinomas and matched normal adjacent tissues to evaluate the expression of peroxisome proliferator-activated receptor delta, cyclooxygenase-2, vascular endothelial growth factor-A, and CD34 through immunohistochemical analysis. Peroxisome proliferator-activated receptor delta was expressed in 25 (48.1%), and cyclooxygenase-2 was expressed in 26 (50.0%) of total colorectal cancer tissues. Tissue samples were divided into four groups, according to the expression of peroxisome proliferator-activated receptor delta and cyclooxygenase-2. The positive rate of vascular endothelial growth factor-A, the levels of microvascular density, and the incidence of venous vessel invasion in peroxisome proliferator-activated receptor delta (+)/cyclooxygenase-2 (+) samples exceeded significantly those in the other three groups of tissue samples (P < 0.05). The results suggest that the axis of the cyclooxygenase-2/peroxisome proliferator-activated receptor delta signal pathway might play a crucial role in the development of colorectal cancers by enhancing angiogenesis.

Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: from orphan receptors to drug discovery. J Med Chem. 2000;43:527–550. doi:10.1021/jm990554g.PubMedCrossRef

Kliewer SA, Forman BM, Blumberg B, et al. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proc Natl Acad Sci USA. 1994;91:7355–7359. doi:10.1073/pnas.91.15.7355.PubMedCrossRef

Kliewer SA, Lehmann JM, Milburn MV, Willson TM. The PPARs and PXRs: nuclear xenobiotic receptors that define novel hormone signaling pathways. Recent Prog Horm Res. 2000;54:345–367.

Spiegelman BM. PPAR-gamma: adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998;47:507–514. doi:10.2337/diabetes.47.4.507.PubMedCrossRef

Peters JM, Cattley RC, Gonzalez FJ. Role of PPAR alpha in the mechanism of action of the nongenotoxic carcinogen and peroxisome proliferator Wy-14,643. Carcinogenesis. 1997;18:2029–2033. doi:10.1093/carcin/18.11.2029.PubMedCrossRef

Reddy JK, Chu R. Peroxisome proliferator-induced pleiotropic responses: pursuit of a phenomenon. Ann NY Acad Sci. 1996;804:176–201. doi:10.1111/j.1749-6632.1996.tb18616.x.PubMedCrossRef

Tontonoz P, Singer S, Forman BM, et al. Terminal differentiation of human liposarcoma cells induced by ligands for peroxisome proliferator-activated receptor gamma and the retinoid X receptor. Proc Natl Acad Sci USA. 1997;94:237–241. doi:10.1073/pnas.94.1.237.PubMedCrossRef

Mueller E, Sarraf P, Tontonoz P, et al. Terminal differentiation of human breast cancer through PPAR gamma. Mol Cell. 1998;1:465–470. doi:10.1016/S1097-2765(00)80047-7.PubMedCrossRef

Sarraf P, Mueller E, Jones D, et al. Differentiation and reversal of malignant changes in colon cancer through PPAR gamma. Nat Med. 1998;4:1046–1052. doi:10.1038/2030.PubMedCrossRef

10.

Brockman JA, Gupta RA, DuBois RN. Activation of PPAR gamma leads to inhibition of anchorage-independent growth of human colorectal cancer cells. Gastroenterology. 1998;115:1049–1055. doi:10.1016/S0016-5085(98)70072-1.PubMedCrossRef

11.

He TC, Chan TA, Vogelstein B, Kinzler KW. PPARd is an APC regulated target of nonsteroidal anti-inflammatory drugs. Cell. 1999;99:335–345. doi:10.1016/S0092-8674(00)81664-5.PubMedCrossRef

12.

Gupta RA, Wang D, Katkuri S, Wang H, Dey SK, DuBois RN. Activation of nuclear hormone receptor peroxisome proliferator-activated receptor-d accelerates intestinal adenoma growth. Nat Med. 2004;10:245–247. doi:10.1038/nm993.PubMedCrossRef

13.

Takayama O, Yamamoto H, Damdinsuren B, et al. Expression of PPARd in multistage carcinogenesis of the colorectum: implications of malignant cancer morphology. Br J Cancer. 2006;95:889–895. doi:10.1038/sj.bjc.6603343.PubMedCrossRef

14.

Harman FS, Nicol CJ, Marin HE, Ward JM, Gonzalez FJ, Peters JM. Peroxisome proliferator-activated receptor-d attenuates colon carcinogenesis. Nat Med. 2004;10:481–483. doi:10.1038/nm1026.PubMedCrossRef

15.

Reed KR, Sansom OJ, Hayes AJ, et al. PPAR delta status and Apc-mediated tumorigenesis in the mouse intestine. Oncogene. 2004;23:8992–8996. doi:10.1038/sj.onc.1208143.PubMedCrossRef

16.

Park BH, Vogelstein B, Kinzler KW. Genetic disruption of PPARd decreases the tumorigenicity of human colon cancer cells. Proc Natl Acad Sci USA. 2001;98:2598–2603. doi:10.1073/pnas.051630998.PubMedCrossRef

17.

Bergsland EK. Vascular endothelial growth factor as a therapeutic target in cancer. Am J Health Syst Pharm. 2004;61:S4–S11.PubMed

18.

Wang D, Wang H, Guo Y, et al. Crosstalk between peroxisome proliferator-activated receptor delta and VEGF stimulates cancer progression. Proc Natl Acad Sci USA. 2006;103:19069–19074. doi:10.1073/pnas.0607948103.PubMedCrossRef

19.

Cutler NS, Graves-Deal R, LaFleur BJ, et al. Stromal production of prostacyclin confers an antiapoptotic effect to colonic epithelial cells. Cancer Res. 2003;63:1748–1751.PubMed

20.

Wang D, Mann JR, DuBois RN. WNT and cyclooxygenase-2 crosstalk accelerates adenoma growth. Cell Cycle. 2004;3:1512–1515.PubMed

21.

Wang D, Wang H, Shi Q, et al. Prostaglandin E(2) promotes colorectal adenoma growth via transactivation of the nuclear peroxisome proliferator-activated receptor delta. Cancer Cell. 2004;6:285–295. doi:10.1016/j.ccr.2004.08.011.PubMedCrossRef

22.

Gupta RA, Tan J, Krause WF, et al. Prostacyclin-mediated activation of peroxisome proliferator-activated receptor delta in colorectal cancer. Proc Natl Acad Sci USA. 2000;97:13275–13280. doi:10.1073/pnas.97.24.13275.PubMedCrossRef

23.

Piqueras L, Reynolds AR, Hodivala-Dilke KM, et al. Activation of PPAR beta/delta induces endothelial cell proliferation and angiogenesis. Arterioscler Thromb Vasc Biol. 2007;27:63–69. doi:10.1161/01.ATV.0000250972.83623.61.PubMedCrossRef

24.

Yonenaga Y, Mori A, Onodera H, et al. Absence of smooth muscle actin-positive pericyte coverage of tumor vessels correlates with hematogenous metastasis and prognosis of colorectal cancer patients. Oncology. 2005;69:159–166. doi:10.1159/000087840.PubMedCrossRef

25.

Onogawa S, Tanaka S, Oka S, et al. Clinical significance of angiogenesis in rectal carcinoid tumors. Oncol Rep. 2002;9:489–494.PubMed

26.

Takebayashi Y, Aklyama S, Yamada K, Akiba S, Aikou T. Angiogenesis as an unfavorable prognostic factor in human colorectal carcinoma. Cancer. 1996;78:226–231. doi :10.1002/(SICI)1097-0142(19960715)78:2<226::AID-CNCR6>3.0.CO;2-J.

27.

Rmali KA, Puntis MC, Jiang WG. Prognostic values of tumor endothelial markers in patients with colorectal cancer. World J Gastroenterol. 2005;11:1283–1286.PubMed

28.

Choi HJ, Hyun MS, Jung GJ, Kim SS, Hong SH. Tumor angiogenesis as a prognostic predictor in colorectal carcinoma with special reference to mode of metastasis and recurrence. Oncology. 1998;55:575–581. doi:10.1159/000011915.PubMedCrossRef

29.

Acikalin MF, Oner U, Topcu I, Yasar B, Kiper H, Colak E. Tumor angiogenesis and mast cell density in the prognostic assessment of colorectal carcinomas. Dig Liver Dis. 2005;37:162–169. doi:10.1016/j.dld.2004.09.028.PubMedCrossRef

30.

Engel CJ, Bennett ST, Chambers AF, Doig GS, Kerkvliet N, O’Malley FP. Tumor angiogenesis predicts recurrence in invasive colorectal cancer when controlled for Dukes staging. Am J Surg Pathol. 1996;20:1260–1265. doi:10.1097/00000478-199610000-00012.PubMedCrossRef

31.

Frank RE, Saclarides TJ, Leurgans S, Speziale NJ, Drab EA, Rubin DB. Tumor angiogenesis as a predictor of recurrence and survival in patients with node-negative colon cancer. Ann Surg. 1995;222:695–699. doi:10.1097/00000658-199512000-00002.PubMedCrossRef

32.

Jubb AM, Hurwitz HI, Bai W, et al. Impact of vascular endothelial growth factor-A expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer. J Clin Oncol. 2006;24:217–227. doi:10.1200/JCO.2005.01.5388.PubMedCrossRef

33.

Bossi P, Viale G, Lee AK, Alfano R, Coggi G, Bosari S. Angiogenesis in colorectal tumors: microvessel quantitation in adenomas and carcinomas with clinicopathological correlations. Cancer Res. 1995;55:5049–5053.PubMed

34.

Gunther K, Radkow T, Reymond MA, et al. Angiogenesis and dendritic cell density are not correlated with metachronous distant metastasis in curatively operated rectal cancer. Int J Colorectal Dis. 2003;18:300–308.PubMed

35.

Masunaga R, Kohno H, Dhar DK, et al. Cyclooxygenase-2 expression correlates with tumor neovascularization and prognosis in human colorectal carcinoma patients. Clin Cancer Res. 2000;6:4064–4068.PubMed

36.

Liang P, Nakada I, Hong JW, et al. Prognostic significance of immunohistochemically detected blood and lymphatic vessel invasion in colorectal carcinoma: its impact on prognosis. Ann Surg Oncol. 2007;14:470–477. doi:10.1245/s10434-006-9189-3.PubMedCrossRef

Title: The Simultaneous Expression of Peroxisome Proliferator-Activated Receptor Delta and Cyclooxygenase-2 May Enhance Angiogenesis and Tumor Venous Invasion in Tissues of Colorectal Cancers
Authors: Masahiro Yoshinaga
Yosuke Kitamura
Tomohito Chaen
Shinsaku Yamashita
Satoru Tsuruta
Teruaki Hisano
Yoichi Ikeda
Hironori Sakai
Kazuhiko Nakamura
Ryoichi Takayanagi
Yoichi Muto
Publication date: 01-05-2009
Publisher: Springer US
Published in: Digestive Diseases and Sciences / Issue 5/2009
Print ISSN: 0163-2116
Electronic ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-008-0465-x

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 5/2009

Azithromycin Reduces Gastroesophageal Reflux and Aspiration in Lung Transplant Recipients

Taurocholate Potentiates Ethanol-Induced NF-κB Activation and Inhibits Caspase-3 Activity in Cultured Rat Gastric Mucosal Cells

Troubles with Stomach Bubbles? Or Not?

Effect of Preoperative Intravenous Pantoprazole in Elective-Surgery Patients: A Pilot Study

Synaptic Plasticity: The New Explanation of Visceral Hypersensitivity in Rats with Trichinella spiralis Infection?

Independent Factors Associated with Recurrent Bleeding in Cirrhotic Patients with Esophageal Variceal Hemorrhage

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials