Role of Chemokine Network in the Development and Progression of Ovarian Cancer: a Potential Novel Pharmacological Target

Overview

Journal J Oncol

Specialty Oncology

Date 2010 Jan 6

PMID 20049170

Citations 37

Authors

Federica Barbieri

Adriana Bajetto

Tullio Florio

Affiliations

Soon will be listed here.

Abstract

Ovarian cancer is the most common type of gynecologic malignancy. Despite advances in surgery and chemotherapy, the survival rate is still low since most ovarian cancers relapse and become drug-resistant. Chemokines are small chemoattractant peptides mainly involved in the immune responses. More recently, chemokines were also demonstrated to regulate extra-immunological functions. It was shown that the chemokine network plays crucial functions in the tumorigenesis in several tissues. In particular the imbalanced or aberrant expression of CXCL12 and its receptor CXCR4 strongly affects cancer cell proliferation, recruitment of immunosuppressive cells, neovascularization, and metastasization. In the last years, several molecules able to target CXCR4 or CXCL12 have been developed to interfere with tumor growth, including pharmacological inhibitors, antagonists, and specific antibodies. This chemokine ligand/receptor pair was also proposed to represent an innovative therapeutic target for the treatment of ovarian cancer. Thus, a thorough understanding of ovarian cancer biology, and how chemokines may control these different biological activities might lead to the development of more effective therapies. This paper will focus on the current biology of CXCL12/CXCR4 axis in the context of understanding their potential role in ovarian cancer development.

Citing Articles

Chemokine expression in patients with ovarian cancer or benign ovarian tumors.

Nowak M, Janas L, Soja M, Glowacka E, Szyllo K, Misiek M Arch Med Sci. 2022; 18(3):682-689.

PMID: 35591828 PMC: 9102528. DOI: 10.5114/aoms/110672.

High ratio of pCXCR4/CXCR4 tumor infiltrating immune cells in primary high grade ovarian cancer is indicative for response to chemotherapy.

Walther F, Berther J, Lalos A, Ramser M, Eichelberger S, Mechera R BMC Cancer. 2022; 22(1):376.

PMID: 35397601 PMC: 8994232. DOI: 10.1186/s12885-022-09374-x.

(5E,7E)-4,5,6 Trihydroxy-3-(hydroxymethyl)tetrahydro-2H-pyran-2-ylheptadeca-5,7-dienoate from (L.) Inhibits Ovarian Cancer Cell Growth by Controlling Apoptotic and Metastatic Signaling Mechanisms.

Palanisamy C, Cui B, Zhang H, Jayaraman S, Rajagopal P, Veeraraghavan V Bioinorg Chem Appl. 2022; 2022:4464056.

PMID: 35132312 PMC: 8817890. DOI: 10.1155/2022/4464056.

Fluid shear stress-induced IL-8/CXCR signaling in human ovarian cancer cells.

Sun L, Wen J, Wang L, Wen Q, Wu J, Bie M Transl Cancer Res. 2022; 8(4):1591-1601.

PMID: 35116902 PMC: 8798993. DOI: 10.21037/tcr.2019.08.22.

Antibacterial Activity of T22, a Specific Peptidic Ligand of the Tumoral Marker CXCR4.

Serna N, Carratala J, Conchillo-Sole O, Martinez-Torro C, Unzueta U, Mangues R Pharmaceutics. 2021; 13(11).

PMID: 34834337 PMC: 8621837. DOI: 10.3390/pharmaceutics13111922.

References

Pils D, Pinter A, Reibenwein J, Alfanz A, Horak P, Schmid B . In ovarian cancer the prognostic influence of HER2/neu is not dependent on the CXCR4/SDF-1 signalling pathway. Br J Cancer. 2007; 96(3):485-91. PMC: 2360022. DOI: 10.1038/sj.bjc.6603581. View

Milliken D, Scotton C, Raju S, Balkwill F, Wilson J . Analysis of chemokines and chemokine receptor expression in ovarian cancer ascites. Clin Cancer Res. 2002; 8(4):1108-14. View

Szotek P, Pieretti-Vanmarcke R, Masiakos P, Dinulescu D, Connolly D, Foster R . Ovarian cancer side population defines cells with stem cell-like characteristics and Mullerian Inhibiting Substance responsiveness. Proc Natl Acad Sci U S A. 2006; 103(30):11154-9. PMC: 1544057. DOI: 10.1073/pnas.0603672103. View

Almofti A, Uchida D, Begum N, Tomizuka Y, Iga H, Yoshida H . The clinicopathological significance of the expression of CXCR4 protein in oral squamous cell carcinoma. Int J Oncol. 2004; 25(1):65-71. View

Zhang J, Lu W, Ye F, Chen H, Zhou C, Xie X . Study on CXCR4/SDF-1alpha axis in lymph node metastasis of cervical squamous cell carcinoma. Int J Gynecol Cancer. 2007; 17(2):478-83. DOI: 10.1111/j.1525-1438.2007.00786.x. View

van der Burg M . Advanced ovarian cancer. Curr Treat Options Oncol. 2002; 2(2):109-18. DOI: 10.1007/s11864-001-0053-1. View

Kajiyama H, Shibata K, Terauchi M, Ino K, Nawa A, Kikkawa F . Involvement of SDF-1alpha/CXCR4 axis in the enhanced peritoneal metastasis of epithelial ovarian carcinoma. Int J Cancer. 2007; 122(1):91-9. DOI: 10.1002/ijc.23083. View

Takenaga M, Tamamura H, Hiramatsu K, Nakamura N, Yamaguchi Y, Kitagawa A . A single treatment with microcapsules containing a CXCR4 antagonist suppresses pulmonary metastasis of murine melanoma. Biochem Biophys Res Commun. 2004; 320(1):226-32. DOI: 10.1016/j.bbrc.2004.05.155. View

Molyneaux K, Zinszner H, Kunwar P, Schaible K, Stebler J, Sunshine M . The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival. Development. 2003; 130(18):4279-86. DOI: 10.1242/dev.00640. View

10.

Scotton C, Wilson J, Scott K, Stamp G, Wilbanks G, Fricker S . Multiple actions of the chemokine CXCL12 on epithelial tumor cells in human ovarian cancer. Cancer Res. 2002; 62(20):5930-8. View

11.

Kuritzkes D . HIV-1 entry inhibitors: an overview. Curr Opin HIV AIDS. 2009; 4(2):82-7. PMC: 2753507. DOI: 10.1097/COH.0b013e328322402e. View

12.

Burger J, Burkle A . The CXCR4 chemokine receptor in acute and chronic leukaemia: a marrow homing receptor and potential therapeutic target. Br J Haematol. 2007; 137(4):288-96. DOI: 10.1111/j.1365-2141.2007.06590.x. View

13.

Burns J, Summers B, Wang Y, Melikian A, Berahovich R, Miao Z . A novel chemokine receptor for SDF-1 and I-TAC involved in cell survival, cell adhesion, and tumor development. J Exp Med. 2006; 203(9):2201-13. PMC: 2118398. DOI: 10.1084/jem.20052144. View

14.

Negus R, Stamp G, Hadley J, Balkwill F . Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines. Am J Pathol. 1997; 150(5):1723-34. PMC: 1858213. View

15.

Freedman R, Ma Q, Wang E, Gallardo S, Gordon I, Shin J . Migration deficit in monocyte-macrophages in human ovarian cancer. Cancer Immunol Immunother. 2007; 57(5):635-45. PMC: 11030061. DOI: 10.1007/s00262-007-0401-5. View

16.

Kim J, Takeuchi H, Lam S, Turner R, Wang H, Kuo C . Chemokine receptor CXCR4 expression in colorectal cancer patients increases the risk for recurrence and for poor survival. J Clin Oncol. 2005; 23(12):2744-53. DOI: 10.1200/JCO.2005.07.078. View

17.

Scala S, Ottaiano A, Ascierto P, Cavalli M, Simeone E, Giuliano P . Expression of CXCR4 predicts poor prognosis in patients with malignant melanoma. Clin Cancer Res. 2005; 11(5):1835-41. DOI: 10.1158/1078-0432.CCR-04-1887. View

18.

Mantovani A, Allavena P, Sozzani S, Vecchi A, Locati M, Sica A . Chemokines in the recruitment and shaping of the leukocyte infiltrate of tumors. Semin Cancer Biol. 2004; 14(3):155-60. DOI: 10.1016/j.semcancer.2003.10.001. View

19.

Balkwill F . The significance of cancer cell expression of the chemokine receptor CXCR4. Semin Cancer Biol. 2004; 14(3):171-9. DOI: 10.1016/j.semcancer.2003.10.003. View

20.

De Clercq E . The bicyclam AMD3100 story. Nat Rev Drug Discov. 2003; 2(7):581-7. DOI: 10.1038/nrd1134. View