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
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 a potent innate immune molecule and offers protection against...
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| Format: | Article |
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Frontiers Media S.A.
2020-07-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2020.01171/full |
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| author | Valarmathy Murugaiah Chiara Agostinis Praveen M. Varghese Praveen M. Varghese Beatrice Belmonte Salvatore Vieni Fanan A. Alaql Salman H. Alrokayan Haseeb A. Khan Anuvinder Kaur Terry Roberts Taruna Madan Roberta Bulla Uday Kishore |
| author_facet | Valarmathy Murugaiah Chiara Agostinis Praveen M. Varghese Praveen M. Varghese Beatrice Belmonte Salvatore Vieni Fanan A. Alaql Salman H. Alrokayan Haseeb A. Khan Anuvinder Kaur Terry Roberts Taruna Madan Roberta Bulla Uday Kishore |
| author_sort | Valarmathy Murugaiah |
| collection | DOAJ |
| description | 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 a potent innate immune molecule and offers protection against non-self and altered self, such as pathogens, allergens, and tumor. 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 characterized by varied expressions of estrogen (ER), progesterone (PR), and epidermal growth factor (EGF) receptors (HER2). The cell viability of HER2-overexpressing (SKBR3) and triple-positive (BT474) breast cancer cell lines [but not of a triple-negative cell line (BT20)] was reduced following rfhSP-D treatment at 24 h. 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 caspases 9 and 3 were detected in rfhSP-D-treated BT474 and SKBR3 cells, suggesting an involvement of the intrinsic apoptosis pathway. However, rfhSP-D-induced apoptosis was nullified in the presence of hyaluronic acid (HA) 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 HA showed decreased transcriptional levels of p53 when compared to cells treated with rfhSP-D only. Thus, HA appears to negate the anti-tumorigenic properties of rfhSP-D against HER2-overexpressing and triple-positive breast cancer cells. |
| first_indexed | 2024-12-13T08:46:04Z |
| format | Article |
| id | doaj.art-e7a4cf46ac304622aec46bf9f5ca5cac |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T08:46:04Z |
| publishDate | 2020-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-e7a4cf46ac304622aec46bf9f5ca5cac2022-12-21T23:53:26ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-07-011110.3389/fimmu.2020.01171548401Hyaluronic Acid Present in the Tumor Microenvironment Can Negate the Pro-apototic Effect of a Recombinant Fragment of Human Surfactant Protein D on Breast Cancer CellsValarmathy Murugaiah0Chiara Agostinis1Praveen M. Varghese2Praveen M. Varghese3Beatrice Belmonte4Salvatore Vieni5Fanan A. Alaql6Salman H. Alrokayan7Haseeb A. Khan8Anuvinder Kaur9Terry Roberts10Taruna Madan11Roberta Bulla12Uday Kishore13Biosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United KingdomInstitute for Maternal and Child Health, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Burlo Garofolo, Trieste, ItalyBiosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United KingdomSchool of Biosciences and Technology, Vellore Institute of Technology, Vellore, IndiaTumor Immunology Unit, Human Pathology Section, Department of Health Sciences, University of Palermo, Palermo, ItalyDivision of General and Oncological Surgery, Department of Surgical, Oncological and Oral Sciences, University of Palermo, Palermo, ItalyBiosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United KingdomDepartment of Biochemistry, College of Science, King Saud University, Riyadh, Saudi ArabiaDepartment of Biochemistry, College of Science, King Saud University, Riyadh, Saudi ArabiaBiosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United KingdomBiosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United KingdomDepartment of Innate Immunity, ICMR—National Institute for Research in Reproductive Health, Mumbai, IndiaDepartment of Life Sciences, University of Trieste, Trieste, ItalyBiosciences, College of Health and Life Sciences, Brunel University London, Uxbridge, United KingdomHuman 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 a potent innate immune molecule and offers protection against non-self and altered self, such as pathogens, allergens, and tumor. 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 characterized by varied expressions of estrogen (ER), progesterone (PR), and epidermal growth factor (EGF) receptors (HER2). The cell viability of HER2-overexpressing (SKBR3) and triple-positive (BT474) breast cancer cell lines [but not of a triple-negative cell line (BT20)] was reduced following rfhSP-D treatment at 24 h. 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 caspases 9 and 3 were detected in rfhSP-D-treated BT474 and SKBR3 cells, suggesting an involvement of the intrinsic apoptosis pathway. However, rfhSP-D-induced apoptosis was nullified in the presence of hyaluronic acid (HA) 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 HA showed decreased transcriptional levels of p53 when compared to cells treated with rfhSP-D only. Thus, HA appears to negate the anti-tumorigenic properties of rfhSP-D against HER2-overexpressing and triple-positive breast cancer cells.https://www.frontiersin.org/article/10.3389/fimmu.2020.01171/fullinnate immunitysurfactant protein Dimmune surveillancebreast cancerhyaluronic acid |
| spellingShingle | Valarmathy Murugaiah Chiara Agostinis Praveen M. Varghese Praveen M. Varghese Beatrice Belmonte Salvatore Vieni Fanan A. Alaql Salman H. Alrokayan Haseeb A. Khan Anuvinder Kaur Terry Roberts Taruna Madan Roberta Bulla Uday Kishore 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 innate immunity surfactant protein D immune surveillance breast cancer hyaluronic acid |
| 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | innate immunity surfactant protein D immune surveillance breast cancer hyaluronic acid |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2020.01171/full |
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