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Title: | Hyaluronic Acid Present in the Tumor Microenvironment Can Negate the Pro-apototic Effect of a Recombinant Fragment of Human Surfactant Protein D on Breast Cancer Cells |
Authors: | Murugaiah, V Agostinis, C Varghese, PM Belmonte, B Vieni, S Alaql, F Alrokayan, S Khan, H Kaur, A Roberts, T Madan, T Bulla, R Kishore, U |
Issue Date: | 8-Jul-2020 |
Publisher: | Frontiers Media SA |
Citation: | Murugaiah, V., Agostinis, C., Varghese, P.M., Belmonte, B., Vieni, S., Alaql, F.A., Alrokayan, S.H., Khan, H.A., Kaur, A., Roberts, T., Madan, T., Bulla, R. and Kishore, U. (2020) 'Hyaluronic Acid Present in the Tumor Microenvironment Can Negate the Pro-apototic Effect of a Recombinant Fragment of Human Surfactant Protein D on Breast Cancer Cells', Frontiers in Immunology, 11, 1171, pp. 1-17. doi: 10.3389/fimmu.2020.01171. |
Abstract: | Copyright © 2020 Murugaiah, Agostinis, Varghese, Belmonte, Vieni, Alaql, Alrokayan, Khan, Kaur, Roberts, Madan, Bulla and Kishore. Human surfactant protein D (SP-D) belongs to the family of collectins that is composed of a characteristic amino-terminal collagenous region and a carboxy-terminal C-type lectin domain. Being present at the mucosal surfaces, SP-D acts as is a potent innate immune molecule and offers protection against non-self and altered self-such as pathogens, allergens, and tumour. Here, we examined the effect of a recombinant fragment of human SP-D (rfhSP-D) on a range of breast cancer lines. Breast cancer has four molecular subtypes characterised by varied expression of oestrogen (ER), progesterone (PR) and EGF receptors (HER2). The cell viability of HER2 over-expressing (SKBR3) and triple-positive (BT474) breast cancer cell lines (but not of triple-negative cell line (BT20), was reduced following rfhSP-D treatment at 24h. Upregulation of p21/p27 cell cycle inhibitors and p53 phosphorylation (Ser15) in rfhSP-D-treated BT474 and SKBR3 cell lines signified G2/M cell cycle arrest. Cleaved caspase 9 and 3 were detected in rfhSP-D- treated BT474 and SKBR3 cells, suggesting an involvement of intrinsic apoptosis pathway. However, rfhSP-D-induced apoptosis was nullified in the presence of hyaluronic acid whose increased level in breast tumor microenvironment is associated with malignant tumor progression and invasion. rfhSP-D bound to solid-phase HA and promoted tumor cell proliferation. rfhSP-D-treated SKBR3 cells in the presence of hyaluronic acid showed decreased transcriptional levels of p53 when compared to SKBR3 cells treated with rfhSP-D only. Thus, hyaluronic acid appears to negate the anti-tumorigenic properties of rfhSP-D against HER2-over-expressing and triple-positive breast cancer cells. |
URI: | https://bura.brunel.ac.uk/handle/2438/20829 |
DOI: | https://doi.org/10.3389/fimmu.2020.01171 |
Appears in Collections: | Brunel Library Dept of Life Sciences Research Papers |
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