Research Papers:

Measurements of heterotypic associations between cluster of differentiation CD74 and CD44 in human breast cancer-derived cells

Hussain Al Ssadh, Patrick S. Spencer, Waleed Alabdulmenaim, Rana Alghamdi, Inamul Hasan Madar, Jose M. Miranda-Sayago and Nelson Fernández _

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Oncotarget. 2017; 8:92143-92156. https://doi.org/10.18632/oncotarget.20922

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Hussain Al Ssadh1, Patrick S. Spencer1, Waleed Alabdulmenaim1,2, Rana Alghamdi1,3, Inamul Hasan Madar4, Jose M. Miranda-Sayago1 and Nelson Fernández1

1School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester, Essex CO4 3SQ, United Kingdom

2Pathology Department, College of Medicine, Qassim University, Qassim, Saudi Arabia

3King Abdulaziz University, Rabigh Campus, Rabigh, Saudi Arabia

4Department of Biotechnology and Genetic Engineering, Bharathidasan University, Tiruchirappalli, 620024, Tamil Nadu, India

Correspondence to:

Nelson Fernández, email: [email protected]

Keywords: CD74, CD44s, CD44v, co-localization

Received: May 23, 2017     Accepted: August 17, 2017     Published: September 14, 2017


Interactions between pairs of membrane-bound receptors can enhance tumour development with implications for targeted therapies for cancer. Here we demonstrate clear heterotypic interaction between CD74 and CD44, which might act in synergy and hence contribute to breast cancer progression. CD74, a type II transmembrane glycoprotein, is a chaperone for MHC class II biosynthesis and a receptor for the MIF. CD44 is the receptor for hyaluronic acid and is a Type I transmembrane protein. Interactions between CD74, MIF and the intra-cytoplasmic domain of CD44 result in activation of ERK1/2 pathway, leading to increased cell proliferation and decreased apoptosis. The level of CD44 in the breast tumor cell lines CAMA-1, MDA-MB-231, MDA-MB-435 and the immortalized normal luminal cell line 226LDM was higher than that of CD74. It was also observed that CD74 and CD44 exhibit significant variation in expression levels across the cells. CD74 and CD44 were observed to accumulate in cytoplasmic compartments, suggesting they associate with each other to facilitate tumour growth and metastasis. Use of a novel and validated colocalisation and image processing approach, coupled with co-immunoprecipitation, confirmed that CD74 and CD44 physically interact, suggesting a possible role in breast tumour growth. This is the first time that CD74 and CD44 colocalization has been quantified in breast cancer cells using a non-invasive and validated bioimaging procedure. Measuring the co-expression levels of CD74 and CD44 could potentially be used as a ‘biomarker signature’ to monitor different stages of breast cancer.

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