Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

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.
ADVANCED SEARCH
Log in
Top
Cancer Cell International
Published in: Cancer Cell International 1/2006

Open Access 01-12-2006 | Primary research

Expression of platelet derived growth factor family members and the potential role of imatinib mesylate for cervical cancer

Authors: Lucia Taja-Chayeb, Alma Chavez-Blanco, Jorge Martínez-Tlahuel, Aurora González-Fierro, Myrna Candelaria, Jose Chanona-Vilchis, Elizabeth Robles, Alfonso Dueñas-Gonzalez

Published in: Cancer Cell International | Issue 1/2006

Login to get access

Abstract

Background

Despite significant achievements in the treatment of cervical cancer, it is still a deadly disease; hence newer therapeutical modalities are needed. Preliminary investigations suggest that platelet-derived growth factor (PDGF) might have a role in the development of cervical cancer, therefore it is important to determine whether this growth factor pathway is functional and its targeting with imatinib mesylate leads to growth inhibition of cervical cancer cells.

Results

PDGF receptors (PDGFR) and their ligands are frequently expressed in cervical cancer and the majority exhibited a combination of family members co-expression. A number of intronic and exonic variations but no known mutations in the coding sequence of the PDGFRα gene were found in cancer cell lines and primary tumors. Growth assays demonstrated that PDGFBB induces growth stimulation that can be blocked by imatinib and that this tyrosine kinase inhibitor on its own inhibits cell growth. These effects were associated with the phosphorylation status of the receptor.

Conclusion

The PDGFR system may have a role in the pathogenesis of cervical cancer as their members are frequently expressed in this tumor and cervical cancer lines are growth inhibited by the PDGFR antagonist imatinib.
Appendix
Available only for authorised users
Literature
1.
Parkin DM, Bray F, Ferlay J, Pisani P: Estimating the world cancer burden: Globocan 2000. Int J Cancer. 2001, 94: 153-156. 10.1002/ijc.1440.CrossRefPubMed
2.
Snijders PJ, Steenbergen RD, Heideman DA, Meijer CJ: HPV-mediated cervical carcinogenesis: concepts and clinical implications. J Pathol. 2006, 208: 152-164. 10.1002/path.1866.CrossRefPubMed
3.
Kersemaekers AM, van de Vijver MJ, Kenter GG, Fleuren GJ: Genetic alterations during the progression of squamous cell carcinomas of the uterine cervix. Genes Chromosomes Cancer. 1999, 26: 346-354. 10.1002/(SICI)1098-2264(199912)26:4<346::AID-GCC9>3.0.CO;2-D.CrossRefPubMed
4.
Duenas-Gonzalez A, Lizano M, Candelaria M, Cetina L, Arce C, Cervera E: Epigenetics of cervical cancer. An overview and therapeutic perspectives. Mol Cancer. 2005, 4: 38-10.1186/1476-4598-4-38.PubMedCentralCrossRefPubMed
5.
Vaidya AP, Parnes AD, Seiden MV: Rationale and clinical experience with epidermal growth factor receptor inhibitors in gynecologic malignancies. Curr Treat Options Oncol. 2005, 6: 103-114.CrossRefPubMed
6.
Ostman A: PDGF receptors-mediators of autocrine tumor growth and regulators of tumor vasculature and stroma. Cytokine Growth Factor Rev. 2004, 15: 275-286. 10.1016/j.cytogfr.2004.03.002.CrossRefPubMed
7.
Yu J, Ustach C, Kim HR: Platelet-derived growth factor signaling and human cancer. J Biochem Mol Biol. 2003, 36: 49-59.CrossRefPubMed
8.
George D: Platelet-derived growth factor receptors: a therapeutic target in solid tumors. Semin Oncol. 2001, 28 (5 Suppl 17): 27-33. 10.1053/sonc.2001.29185.CrossRefPubMed
9.
Heldin C-H, Westermark B: Mechanism of action and in vivo role of platelet-derived growth factor. Physiol Rev. 1999, 79: 1283-1316.PubMed
10.
Li X, Ponten A, Aase K, Karlsson L, Abramsson A, Uutela M, Backstrom G, Hellstrom M, Bostrom H, Li H, Soriano P, Betsholtz C, Heldin CH, Alitalo K, Ostman A, Eriksson U: PDGF-C is a new protease-activated ligand for the PDGF alpha-receptor. Nat Cell Biol. 2000, 2: 302-309. 10.1038/35010579.CrossRefPubMed
11.
Bergsten E, Uutela M, Li X, Pietras K, Ostman A, Heldin CH, Alitalo K, Eriksson U: PDGF-D is a specific, protease-activated ligand for the PDGF beta-receptor. Nat Cell Biol. 2001, 3: 512-516. 10.1038/35074588.CrossRefPubMed
12.
Reigstad LJ, Varhaug JE, Lillehaug JR: Structural and functional specificities of PDGF-C and PDGF-D, the novel member of the platelet-derived growth factors family. FEBS J. 2005, 272: 5723-5741. 10.1111/j.1742-4658.2005.04989.x.CrossRefPubMed
13.
Heldin CH, Eriksson U, Östman A: New members of the platelet-derived growth factor family of mitogens. Arch Biochem Biophys. 2002, 398: 284-290. 10.1006/abbi.2001.2707.CrossRefPubMed
14.
Buchdunger E, O'Reilly T, Wood J: Pharmacology of imatinib (STI571). Eur J Cancer. 2002, 38 (Suppl 5): S28-S36. 10.1016/S0959-8049(02)80600-1.CrossRefPubMed
15.
Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB: Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med. 1996, 2: 561-566. 10.1038/nm0596-561.CrossRefPubMed
16.
Carroll M, Ohno-Jones S, Tamura S, Buchdunger E, Zimmermann J, Lydon NB, Gilliland DG, Druker BJ: CGP 5 a tyrosine kinase inhibitor, inhibits the growth of cells expressing BCR-ABL, TEL-ABL, and TEL-PDGFR fusion proteins. Blood. 1997, 90: 4947-4952.PubMed
17.
Board R, Jayson GC: Platelet-derived growth factor receptor (PDGFR): a target for anticancer therapeutics. Drug Resist Updat. 2005, 8: 75-83. 10.1016/j.drup.2005.03.004.CrossRefPubMed
18.
Petti L, DiMaio D: Stable association between the bovine papillomavirus E5 transforming protein and activated platelet-derived growth factor receptor in transformed mouse cells. Proc Natl Acad Sci USA. 1992, 89: 6736-6740. 10.1073/pnas.89.15.6736.PubMedCentralCrossRefPubMed
19.
Nilson LA, DiMaio D: Platelet-derived growth factor receptor can mediate tumorigenic transformation by the bovine papillomavirus E5 protein. Mol Cell Biol. 1993, 13: 4137-4145.PubMedCentralCrossRefPubMed
20.
Drummond-Barbosa DA, Vaillancourt RR, Kazlauskas A, DiMaio D: Ligand-independent activation of the platelet-derived growth factor beta receptor: requirements for bovine papillomavirus E5-induced mitogenic signaling. Mol Cell Biol. 1995, 15: 2570-2581.PubMedCentralCrossRefPubMed
21.
Nappi VM, Petti LM: Multiple transmembrane amino acid requirements suggest a highly specific interaction between the bovine papillomavirus E5 oncoprotein and the platelet-derived growth factor beta receptor. J Virol. 2002, 76: 7976-7986. 10.1128/JVI.76.16.7976-7986.2002.PubMedCentralCrossRefPubMed
22.
Mayer TJ, Frauenhoffer EE, Meyers AC: Expression of epidermal growth factor and platelet-derived growth factor receptors during cervical carcinogenesis. In Vitro Cell Dev Biol Anim. 2000, 36: 667-676. 10.1290/1071-2690(2000)036<0667:EOEGFA>2.0.CO;2.CrossRefPubMed
23.
Heuchel R, Berg A, Tallquist M, Ahlen K, Reed RK, Rubin K, Claesson-Welsh L, Heldin CH, Soriano P: Platelet-derived growth factor beta receptor regulates interstitial fluid homeostasis through phosphatidylinositol-3' kinase signaling. Proc Natl Acad Sci USA. 1999, 96: 11410-11415. 10.1073/pnas.96.20.11410.PubMedCentralCrossRefPubMed
24.
Milosevic M, Fyles A, Hill R: Interstitial fluid pressure in cervical cancer: guide to targeted therapy. Am J Clin Oncol. 2001, 24: 516-521. 10.1097/00000421-200110000-00020.CrossRefPubMed
25.
Pietras K, Ostman A, Sjoquist M, Buchdunger E, Reed RK, Heldin CH, Rubin K: Inhibition of platelet-derived growth factor receptors reduces interstitial hypertension and increases transcapillary transport in tumor. Cancer Res. 2001, 61: 2929-2934.PubMed
26.
Roh HD, Boucher Y, Kalnicki S, Buchsbaum R, Bloomer WD, Jain RK: Interstitial hypertension in carcinoma of uterine cervix in patients: possible correlation with tumor oxygenation and radiation response. Cancer Res. 1991, 51: 6695-6698.PubMed
27.
Milosevic M, Fyles A, Hedley D, Pintilie M, Levin W, Manchul L, Hill R: Interstitial fluid pressure predicts survival in patients with cervix cancer independent of clinical prognostic factors and tumor oxygen measurements. Cancer Res. 2001, 61: 6400-6405.PubMed
28.
Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffitj DJ, Haley A, Town A, Demetri GD, Fletcher CD, Fletcher JA: PDGFRA activating mutations in gastrointestinal tumors. Science. 2003, 299: 708-710. 10.1126/science.1079666.CrossRefPubMed
29.
Corless CL, Schroeder A, Griffith D, Town A, McGreevey L, Harrell P, Shiraga S, Bainbridge T, Morich J, Heinrich MC: PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol. 2005, 23: 5357-5364. 10.1200/JCO.2005.14.068.CrossRefPubMed
30.
Ishiyama M, Tominaga H, Shiga M, Sasamoto K, Ohkura Y, Ueno K: A combined assay of cell viability and in vitro cytotoxicity with a highly water-soluble tetrazolium salt, neutral red and crystal violet. Biol Pharm Bull. 1996, 19: 1518-1520.CrossRefPubMed
31.
Dueñas-Gonzalez A, Cetina L, Mariscal I, de la Garza J: Modern management of locally advanced cervical carcinoma. Cancer Treat Rev. 2003, 29: 389-399. 10.1016/S0305-7372(03)00068-9.CrossRefPubMed
32.
Duenas-Gonzalez A, Cetina-Perez L, Lopez-Graniel C, Gonzalez-Enciso A, Gomez-Gonzalez E, Rivera-Rubi L, Montalvo-Esquivel G, Munoz-Gonzalez D, Robles-Flores J, Vazquez-Govea E, de La Garza J, Mohar A: Pathologic response and toxicity assessment of chemoradiotherapy with cisplatin versus cisplatin plus gemcitabine in cervical cancer: a randomized Phase II study. Int J Radiat Oncol Biol Phys. 2005, 61: 817-823. 10.1016/j.ijrobp.2004.07.676.CrossRefPubMed
33.
Long HJ, Bundy BN, Grendys EC, Benda JA, McMeekin DS, Sorosky J, Miller DS, Eaton LA, Fiorica JV, Gynecologic Oncology Group Study: Randomized phase III trial of cisplatin with or without topotecan in carcinoma of the uterine cervix: a Gynecologic Oncology Group Study. J Clin Oncol. 2005, 23: 4626-4633. 10.1200/JCO.2005.10.021.CrossRefPubMed
34.
35.
Dy GK, Miller AA, Mandrekar SJ, Aubry MC, Langdon RM, Morton RF, Schild SE, Jett JR, Adjei AA: A phase II trial of imatinib (ST1571) in patients with c-kit expressing relapsed small-cell lung cancer: a CALGB and NCCTG study. Ann Oncol. 2005, 16: 1811-1816. 10.1093/annonc/mdi365.CrossRefPubMed
36.
Rao K, Goodin S, Levitt MJ, Dave N, Shih WJ, Lin Y, Capanna T, Doyle-Lindrud S, Juvidian P, DiPaola RS: A phase II trial of imatinib mesylate in patients with prostate specific antigen progression after local therapy for prostate cancer. Prostate. 2005, 62: 115-122. 10.1002/pros.20130.CrossRefPubMed
37.
Krug LM, Crapanzano JP, Azzoli CG, Miller VA, Rizvi N, Gomez J, Kris MG, Pizzo B, Tyson L, Dunne M, Heelan RT: Imatinib mesylate lacks activity in small cell lung carcinoma expressing c-kit protein: a phase II clinical trial. Cancer. 2005, 103: 2128-2131. 10.1002/cncr.21000.CrossRefPubMed
38.
Matei D, Emerson RE, Lai YC, Baldridge LA, Rao J, Yiannoutsos C, Donner DD: Autocrine activation of PDGFR alpha promotes the progression of ovarian cancer. Oncogene. 2006, 25: 2060-2069. 10.1038/sj.onc.1209232.CrossRefPubMed
39.
Forsberg K, Valyi-Nagy I, Heldin CH, Herlyn M, Westermark B: Platelet-derived growth factor (PDGF) in oncogenesis: development of a vascular connective tissue stroma in xenotransplanted human melanoma producing PDGF-BB. Proc Natl Acad Sci USA. 1993, 90: 393-397. 10.1073/pnas.90.2.393.PubMedCentralCrossRefPubMed
40.
Dong J, Grunstein J, Tejada M, Peale F, Frantz G, Liang WC, Bai W, Yu L, Kowalski J, Liang X, Fuh G, Gerber HP, Ferrara N: VEGF-null cells require PDGFR alpha signaling-mediated stromal fibroblast recruitment for tumorigenesis. EMBO J. 2004, 23: 2800-2810. 10.1038/sj.emboj.7600289.PubMedCentralCrossRefPubMed
41.
Carvalho I, Milanezi F, Martins A, Reis RM, Schmitt F: Overexpression of platelet-derived growth factor receptor alpha in breast cancer is associated with tumour progression. Breast Cancer Res. 2005, 7: R788-R795. 10.1186/bcr1304.PubMedCentralCrossRefPubMed
42.
Lasota J, Dansonka-Mieszkowska A, Sobin LH, Miettinen M: A great majority of GISTs with PDGFRA mutations represent gastric tumors of low or no malignant potential. Lab Invest. 2004, 84: 874-883. 10.1038/labinvest.3700122.CrossRefPubMed
43.
44.
Tchernitchko D, Goossens M, Wajcman H: In silico prediction of the deleterious effect of a mutation: proceed with caution in clinical genetics. Clin Chem. 2004, 50: 1974-1978. 10.1373/clinchem.2004.036053.CrossRefPubMed
45.
McGary EC, Weber K, Mills L, Doucet M, Lewis V, Lev DC, Fidler IJ, Bar-Eli M: Inhibition of platelet-derived growth factor-mediated proliferation of osteosarcoma cells by the novel tyrosine kinase inhibitor STI571. Clin Cancer Res. 2002, 8: 3584-3591.PubMed
46.
Yu J, Ustach C, Kim HR: Platelet-derived growth factor signaling and human cancer. J Biochem Mol Biol. 2003, 36: 49-59.CrossRefPubMed
Metadata
Title
Expression of platelet derived growth factor family members and the potential role of imatinib mesylate for cervical cancer
Authors
Lucia Taja-Chayeb
Alma Chavez-Blanco
Jorge Martínez-Tlahuel
Aurora González-Fierro
Myrna Candelaria
Jose Chanona-Vilchis
Elizabeth Robles
Alfonso Dueñas-Gonzalez
Publication date
01-12-2006
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2006
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/1475-2867-6-22

Other articles of this Issue 1/2006

Cancer Cell International 1/2006 Go to the issue

Primary research

Expression of EpCAM in uveal melanoma

Primary research

Multicellular Tumour Spheroid as a model for evaluation of [18F]FDG as biomarker for breast cancer treatment monitoring

Primary research

Protease nexin-1 expression is altered in human breast cancer

Hypothesis

Stem cells, senescence, neosis and self-renewal in cancer

Primary research

Antineoplastic effects of the DNA methylation inhibitor hydralazine and the histone deacetylase inhibitor valproic acid in cancer cell lines

Primary research

Antisense oligonucleotide inhibition of hepatitis C virus genotype 4 replication in HepG2 cells
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits