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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
- Source :
- Frontiers in Immunology, Vol 11 (2020), Frontiers in Immunology
- Publication Year :
- 2020
- Publisher :
- Frontiers Media SA, 2020.
-
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. King Saud University, Riyadh, International Scientific Partnership Program (ISPP) ISPP-145; Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy, RC20/16 and 5MILLE15D.
- Subjects :
- lcsh:Immunologic diseases. Allergy
0301 basic medicine
surfactant protein D
Immunology
Collectin
Apoptosis
Breast Neoplasms
03 medical and health sciences
breast cancer
0302 clinical medicine
Epidermal growth factor
Cell Line, Tumor
hyaluronic acid
Tumor Microenvironment
Humans
Immunology and Allergy
skin and connective tissue diseases
innate immunity
Original Research
Tumor microenvironment
Chemistry
immune surveillance
Intrinsic apoptosis
Cell cycle
Pulmonary Surfactant-Associated Protein D
Recombinant Proteins
030104 developmental biology
Cell culture
SKBR3
Cancer research
Female
lcsh:RC581-607
030215 immunology
Subjects
Details
- ISSN :
- 16643224
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Frontiers in Immunology
- Accession number :
- edsair.doi.dedup.....2df9fdeed1a48f8476870c1c33d70d50