The Expression of Leptin and Its Receptor During Tumorigenesis of Diffuse Gliomas Such As Astrocytoma and Oligodendroglioma- Grade II, III and IV (NOS)

Overview

Journal Asian Pac J Cancer Prev

Specialty Oncology

Date 2019 Feb 27

PMID 30803210

Citations 2

Authors

Ramya S Vokuda

Srinivas B H

Venkastesh S Madhugiri

Saravana Kumar Velusamy

Surendra Kumar Verma

Affiliations

Soon will be listed here.

Abstract

Background: Leptin, an adipocytokine functions via the leptin receptor, OB-Rb that contains an intact intracellular domain and activates the JAK/STAT signalling cascade. It stimulates growth, migration and invasion of cancer cells in vitro potentiating angiogenesis. Recently, the involvement of leptin in tumor progression is being explored. Gliomas exhibit poor prognosis, low survival rates demanding for novel therapeutic regimens resulting in discovery of many potential biomarkers and pharmaceutical targets. We analysed the potential role of leptin and OB-Rb in carcinogenesis of malignant gliomas. Methods: Sixty fresh tissue samples of diffuse gliomas were collected after tumor excision. Real time PCR, immunohistochemical (IHC) analysis and western blot analysis were carried out to assess the expression of leptin and its receptor. Results: The present study demonstrates the expression of leptin and LepR and their involvement in tumor progression. Of the 60 cases, 57 cases (95%) and 53 cases (88.3%) showed amplification for leptin and OB-Rb respectively. The expression of these proteins were measured semi-quantitatively and correlated with degree of malignancy (p<0.05). The bands were visualised on western blot. Conclusion: Leptin may be valued as a pharmaceutical target and anti-leptin compounds could be developed as drugs in mono- or combined therapies for these tumors.

Citing Articles

The Modulation of Adipokines, Adipomyokines, and Sleep Disorders on Carcinogenesis.

Brzecka A, Martynowicz H, Daroszewski C, Majchrzak M, Ejma M, Misiuk-Hojlo M J Clin Med. 2023; 12(7).

PMID: 37048738 PMC: 10094938. DOI: 10.3390/jcm12072655.

The Diagnostic and Therapeutic Role of Leptin and Its Receptor ObR in Glioblastoma Multiforme.

Kinfe T, Stadlbauer A, Bozhkov Y, Kremenevski N, Brandner S, Buchfelder M Cancers (Basel). 2020; 12(12).

PMID: 33316976 PMC: 7764087. DOI: 10.3390/cancers12123691.

References

Ishikawa M, Kitayama J, Nagawa H . Enhanced expression of leptin and leptin receptor (OB-R) in human breast cancer. Clin Cancer Res. 2004; 10(13):4325-31. DOI: 10.1158/1078-0432.CCR-03-0749. View

Russo V, Metaxas S, Kobayashi K, Harris M, Werther G . Antiapoptotic effects of leptin in human neuroblastoma cells. Endocrinology. 2004; 145(9):4103-12. DOI: 10.1210/en.2003-1767. View

Riolfi M, Ferla R, Del Valle L, Pina-Oviedo S, Scolaro L, Micciolo R . Leptin and its receptor are overexpressed in brain tumors and correlate with the degree of malignancy. Brain Pathol. 2009; 20(2):481-9. PMC: 2864337. DOI: 10.1111/j.1750-3639.2009.00323.x. View

Han G, Wang L, Zhao W, Yue Z, Zhao R, Li Y . High expression of leptin receptor leads to temozolomide resistance with exhibiting stem/progenitor cell features in gliobalastoma. Cell Cycle. 2013; 12(24):3833-40. PMC: 3905075. DOI: 10.4161/cc.26809. View

Yeh W, Lu D, Lee M, Fu W . Leptin induces migration and invasion of glioma cells through MMP-13 production. Glia. 2008; 57(4):454-64. DOI: 10.1002/glia.20773. View

Kato S, Abarzua-Catalan L, Trigo C, Delpiano A, Sanhueza C, Garcia K . Leptin stimulates migration and invasion and maintains cancer stem-like properties in ovarian cancer cells: an explanation for poor outcomes in obese women. Oncotarget. 2015; 6(25):21100-19. PMC: 4673253. DOI: 10.18632/oncotarget.4228. View

Beales I, Garcia-Morales C, Ogunwobi O, Mutungi G . Adiponectin inhibits leptin-induced oncogenic signalling in oesophageal cancer cells by activation of PTP1B. Mol Cell Endocrinol. 2013; 382(1):150-158. DOI: 10.1016/j.mce.2013.08.013. View

Rene Gonzalez R, Watters A, Xu Y, Singh U, Mann D, Rueda B . Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer. Breast Cancer Res. 2009; 11(3):R36. PMC: 2716504. DOI: 10.1186/bcr2321. View

Unsal M, Kara N, Karakus N, Tural S, Elbistan M . Effects of leptin and leptin receptor gene polymorphisms on lung cancer. Tumour Biol. 2014; 35(10):10231-6. DOI: 10.1007/s13277-014-2293-2. View

10.

Cheng S, Yin P, Hsu Y, Chang Y, Huang S, Lee J . Leptin enhances migration of human papillary thyroid cancer cells through the PI3K/AKT and MEK/ERK signaling pathways. Oncol Rep. 2011; 26(5):1265-71. DOI: 10.3892/or.2011.1388. View

11.

Vokuda R, Srinivas B, Madhugiri V, Verma S . Vascular Endothelial Growth Factor as an Angiogenic Marker in Malignant Astrocytoma and Oligodendroglioma: An Indian Scenario. J Clin Diagn Res. 2017; 11(2):EC05-EC07. PMC: 5376792. DOI: 10.7860/JCDR/2017/24353.9331. View

12.

Ohgaki H . Epidemiology of brain tumors. Methods Mol Biol. 2008; 472:323-42. DOI: 10.1007/978-1-60327-492-0_14. View

13.

Lee K, Choi H, Yang S, Park H, Lee Y, Lee O . The role of leptin in gastric cancer: clinicopathologic features and molecular mechanisms. Biochem Biophys Res Commun. 2014; 446(4):822-9. DOI: 10.1016/j.bbrc.2014.02.072. View

14.

Malendowicz W, Rucinski M, Belloni A, Ziolkowska A, Nussdorfer G, Kwias Z . Real-time PCR analysis of leptin and leptin receptor expression in the rat prostate, and effects of leptin on prostatic acid phosphatase release. Int J Mol Med. 2006; 18(6):1097-100. View

15.

Saxena N, Sharma D, Ding X, Lin S, Marra F, Merlin D . Concomitant activation of the JAK/STAT, PI3K/AKT, and ERK signaling is involved in leptin-mediated promotion of invasion and migration of hepatocellular carcinoma cells. Cancer Res. 2007; 67(6):2497-507. PMC: 2925446. DOI: 10.1158/0008-5472.CAN-06-3075. View

16.

Frankenberry K, Somasundar P, McFadden D, Vona-Davis L . Leptin induces cell migration and the expression of growth factors in human prostate cancer cells. Am J Surg. 2004; 188(5):560-5. DOI: 10.1016/j.amjsurg.2004.07.031. View

17.

Sharma D, Saxena N, Vertino P, Anania F . Leptin promotes the proliferative response and invasiveness in human endometrial cancer cells by activating multiple signal-transduction pathways. Endocr Relat Cancer. 2006; 13(2):629-40. PMC: 2925427. DOI: 10.1677/erc.1.01169. View

18.

Attoub S, Noe V, Pirola L, Bruyneel E, Chastre E, Mareel M . Leptin promotes invasiveness of kidney and colonic epithelial cells via phosphoinositide 3-kinase-, rho-, and rac-dependent signaling pathways. FASEB J. 2000; 14(14):2329-38. DOI: 10.1096/fj.00-0162. View

19.

Jin L, Burguera B, Couce M, Scheithauer B, Lamsan J, Eberhardt N . Leptin and leptin receptor expression in normal and neoplastic human pituitary: evidence of a regulatory role for leptin on pituitary cell proliferation. J Clin Endocrinol Metab. 1999; 84(8):2903-11. DOI: 10.1210/jcem.84.8.5908. View

20.

Rodriguez F, Orr B, Ligon K, Eberhart C . Neoplastic cells are a rare component in human glioblastoma microvasculature. Oncotarget. 2012; 3(1):98-106. PMC: 3292896. DOI: 10.18632/oncotarget.427. View