Oncogenic Roles and Drug Target of CXCR4/CXCL12 Axis in Lung Cancer and Cancer Stem Cell

Overview

Journal Tumour Biol

Publisher Sage Publications

Specialty Oncology

Date 2016 Apr 16

PMID 27079871

Citations 25

Authors

Zhidong Wang

Jian Sun

Yeqian Feng

Xiaocai Tian

Bin Wang

Yong Zhou

Affiliations

Soon will be listed here.

Abstract

Although the great progress has been made in diagnosis and therapeutic in lung cancer, it induces the most cancer death worldwide in both males and females. Chemokines, which have chemotactic abilities, contain up to 50 family members. By binding to G protein-coupled receptors (GPCR), holding seven-transmembrane domain, they function in immune cell trafficking and regulation of cell proliferation, differentiation, activation, and migration, homing under both physiologic and pathologic conditions. The alpha-chemokine receptor CXCR4 for the alpha-chemokine stromal cell-derived-factor-1 (SDF-1) is most widely expressed by tumors. In addition to human tissues of the bone marrow, liver, adrenal glands, and brain, the CXC chemokine SDF-1 or CXCL12 is also highly expressed in lung cancer tissues and is associated with lung metastasis. Lung cancer cells have the capabilities to utilize and manipulate the CXCL12/CXCR system to benefit growth and distant spread. CXCL12/CXCR4 axis is a major culprit for lung cancer and has a crucial role in lung cancer initiation and progression by activating cancer stem cell. This review provides an evaluation of CXCL12/CXCR4 as the potential therapeutic target for lung cancers; it also focuses on the synergistic effects of inhibition of CXCL12/CXCR4 axis and immunotherapy as well as chemotherapy. Together, CXCL12/CXCR4 axis can be a potential therapeutic target for lung cancers and has additive effects with immunotherapy.

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References

Kakarala M, Wicha M . Implications of the cancer stem-cell hypothesis for breast cancer prevention and therapy. J Clin Oncol. 2008; 26(17):2813-20. PMC: 2789399. DOI: 10.1200/JCO.2008.16.3931. View

Otani Y, Kijima T, Kohmo S, Oishi S, Minami T, Nagatomo I . Suppression of metastases of small cell lung cancer cells in mice by a peptidic CXCR4 inhibitor TF14016. FEBS Lett. 2012; 586(20):3639-44. DOI: 10.1016/j.febslet.2012.08.011. View

Nian W, Chen F, Ao X, Chen Z . CXCR4 positive cells from Lewis lung carcinoma cell line have cancer metastatic stem cell characteristics. Mol Cell Biochem. 2011; 355(1-2):241-8. DOI: 10.1007/s11010-011-0860-z. View

Wagner P, Hyjek E, Vazquez M, Meherally D, Liu Y, Chadwick P . CXCL12 and CXCR4 in adenocarcinoma of the lung: association with metastasis and survival. J Thorac Cardiovasc Surg. 2009; 137(3):615-21. DOI: 10.1016/j.jtcvs.2008.07.039. View

Phillips R, Burdick M, Lutz M, Belperio J, Keane M, Strieter R . The stromal derived factor-1/CXCL12-CXC chemokine receptor 4 biological axis in non-small cell lung cancer metastases. Am J Respir Crit Care Med. 2003; 167(12):1676-86. DOI: 10.1164/rccm.200301-071OC. View

Yagui-Beltran A, Jablons D . A translational approach to lung cancer research: From EGFRs to Wnt and cancer stem cells. Ann Thorac Cardiovasc Surg. 2009; 15(4):213-20. PMC: 3066262. View

Zhi Y, Chen J, Zhang S, Chang X, Ma J, Dai D . Down-regulation of CXCL12 by DNA hypermethylation and its involvement in gastric cancer metastatic progression. Dig Dis Sci. 2011; 57(3):650-9. DOI: 10.1007/s10620-011-1922-5. View

Panneerselvam J, Jin J, Shanker M, Lauderdale J, Bates J, Wang Q . IL-24 inhibits lung cancer cell migration and invasion by disrupting the SDF-1/CXCR4 signaling axis. PLoS One. 2015; 10(3):e0122439. PMC: 4361489. DOI: 10.1371/journal.pone.0122439. View

Furuse K, Fukuoka M, Kawahara M, Nishikawa H, Takada Y, Kudoh S . Phase III study of concurrent versus sequential thoracic radiotherapy in combination with mitomycin, vindesine, and cisplatin in unresectable stage III non-small-cell lung cancer. J Clin Oncol. 1999; 17(9):2692-9. DOI: 10.1200/JCO.1999.17.9.2692. View

10.

Reckamp K, Figlin R, Burdick M, Dubinett S, Elashoff R, Strieter R . CXCR4 expression on circulating pan-cytokeratin positive cells is associated with survival in patients with advanced non-small cell lung cancer. BMC Cancer. 2009; 9:213. PMC: 2708193. DOI: 10.1186/1471-2407-9-213. View

11.

Paratore S, Banna G, DArrigo M, Saita S, Iemmolo R, Lucenti L . CXCR4 and CXCL12 immunoreactivities differentiate primary non-small-cell lung cancer with or without brain metastases. Cancer Biomark. 2012; 10(2):79-89. DOI: 10.3233/CBM-2011-0232. View

12.

Williams K, Motiani K, Giridhar P, Kasper S . CD44 integrates signaling in normal stem cell, cancer stem cell and (pre)metastatic niches. Exp Biol Med (Maywood). 2013; 238(3):324-38. PMC: 11037417. DOI: 10.1177/1535370213480714. View

13.

Yen W, Fischer M, Axelrod F, Bond C, Cain J, Cancilla B . Targeting Notch signaling with a Notch2/Notch3 antagonist (tarextumab) inhibits tumor growth and decreases tumor-initiating cell frequency. Clin Cancer Res. 2015; 21(9):2084-95. DOI: 10.1158/1078-0432.CCR-14-2808. View

14.

Quint L, Tummala S, Brisson L, Francis I, Krupnick A, Kazerooni E . Distribution of distant metastases from newly diagnosed non-small cell lung cancer. Ann Thorac Surg. 1996; 62(1):246-50. DOI: 10.1016/0003-4975(96)00220-2. View

15.

Wang J, Li Z, White J, Zhang L . Lung cancer stem cells and implications for future therapeutics. Cell Biochem Biophys. 2014; 69(3):389-98. DOI: 10.1007/s12013-014-9844-4. View

16.

Lennartsson J, Ronnstrand L . Stem cell factor receptor/c-Kit: from basic science to clinical implications. Physiol Rev. 2012; 92(4):1619-49. DOI: 10.1152/physrev.00046.2011. View

17.

Valastyan S, Weinberg R . Tumor metastasis: molecular insights and evolving paradigms. Cell. 2011; 147(2):275-92. PMC: 3261217. DOI: 10.1016/j.cell.2011.09.024. View

18.

Chambers A, Groom A, MacDonald I . Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer. 2002; 2(8):563-72. DOI: 10.1038/nrc865. View

19.

Singla A, Downey C, Bebb G, Jirik F . Characterization of a murine model of metastatic human non-small cell lung cancer and effect of CXCR4 inhibition on the growth of metastases. Oncoscience. 2015; 2(3):263-71. PMC: 4394132. DOI: 10.18632/oncoscience.117. View

20.

Fridrichova I, Smolkova B, Kajabova V, Zmetakova I, Krivulcik T, Mego M . CXCL12 and ADAM23 hypermethylation are associated with advanced breast cancers. Transl Res. 2015; 165(6):717-30. DOI: 10.1016/j.trsl.2014.12.006. View