Probing Transferrin Receptor Overexpression in Gastric Cancer Mice Models

Madeeha Shahzad Lodhi; Muhammad Tahir Khan; Syed Mulazim Hussain Bukhari; Sajjad Hussain Sabir; Zahoor Qadir Samra; Haider Butt; Muhammad Safwan Akram

doi:10.1021/acsomega.1c04382

Probing Transferrin Receptor Overexpression in Gastric Cancer Mice Models

ACS Omega. 2021 Oct 27;6(44):29893-29904. doi: 10.1021/acsomega.1c04382. eCollection 2021 Nov 9.

Authors

Madeeha Shahzad Lodhi^{1

2}, Muhammad Tahir Khan¹, Syed Mulazim Hussain Bukhari³, Sajjad Hussain Sabir⁴, Zahoor Qadir Samra², Haider Butt⁵, Muhammad Safwan Akram^{6

7}

Affiliations

¹ Institute of Molecular Biology and Biotechnology (IMBB), The University of Lahore, KM Defence Road, Lahore 58810, Pakistan.
² Institute of Biochemistry and Biotechnology, University of the Punjab, Lahore 54590, Pakistan.
³ Azad Jammu Kashmir Medical College, Stadium Road, Jalalabad, Muzaffarabad 13100, Pakistan.
⁴ Department of Gastroenterology and Hepatology GHAQ Teaching Hospital, Sahiwal 57000, Pakistan.
⁵ Department of Mechanical Engineering, Khalifa University, P.O. Box 127788, Abu Dhabi 23667, UAE.
⁶ School of Science & Health, Teesside University, Middlesbrough TS1 3BA, U.K.
⁷ National Horizons Centre, Teesside University, 38 John Dixon Ln, Darlington DL1 1HG, U.K.

Abstract

Exposure to carcinogenic chemicals, Helicobacter pylori infection, and high dietary salt are the risk factors associated with gastric cancer. Mice models of gastric cancer are key to understanding the cancer mechanism, to discerning the role played by different factors, and to determining therapeutic effects of different treatments. The goal has been to find targets which are only expressed with cancer so that they can be targeted specifically without harming normal cells. One such target could be the transferrin receptor, a glycoprotein receptor that is expressed many-folds on rapidly growing cells due to the greater demand of iron. In this study, gastric cancer was developed in mice (BALB/c) with human cancer-associated risk factors by feeding them with tumor-inducing concentration of methyl nitrosourea, dietary salt, and H. pylori along with normal feed and water. Three strategies were adopted to induce gastric cancer; (1) use of N-methyl-N-nitrosourea (MNU) with high dietary salt (NaCl), (2) infection with H. pylori (isolated from human gastric tissue), and (3) use of MNU along with high concentration of NaCl after H. pylori infection. Mice were dissected after induction, and histological study of gastric tissue was done with Hematoxylin and Eosin staining. A diagnostic probe comprising transferrin conjugated with cadmium sulfide quantum dots was prepared and characterized. It was used to study the transferrin receptor overexpression in gastric tissue of cancer-induced mice relative to the normal mice. Mice of group 3 showed the highest rate of the cancer incidence ratio (96%) along with a high expression of transferrin receptors among the three groups. Histochemical studies showed that different types of gastric cancer depend upon the cancer-induction conditions. The mouse model of group 3 has the potential to be used in the future to study the therapeutic effects of cancer medicines, and overexpression of transferrin receptors could be identified through the designed probe to be used as diagnostics.