Our objectives were to investigate the interactions between mammary cancer epithelial cells (MCF-7) and stromal cells (Hs-578Bst) at the level of the expression and inhibition of steroidogenesis enzymes by using monolayer and three dimensional co-culture models. Expressions of steroidogenesis enzymes and E2/DHT conversions in co-cultured MCF-7 and Hs-578Bst cells as well as the effects of aromatase inhibitor combined to steroid sulfatase (STS) and 17β-hydroxysteroid dehydrogenases (17βHSDs) inhibitors were evaluated. 17β-HSD type 7 was mostly modulated in MCF-7 cells whereas aromatase was mostly regulated in Hs578Bst cells thereby increasing E2 conversion and MCF-7 cell growth. A combination of inhibitors toward aromatase, STS and 17β-HSD7, was found to be the most significant treatment in decreasing E2 and elevating DHT thus inhibiting MCF-7 cell proliferation and spheroid-like cancer cell aggregation in collagen gel. The interactions between those cells modulated E2 formation in paracrine/intracrine manners by synergistically regulating aromatase, 17β-HSD7 and STS. Among tumor-associated cells, stromal fibroblasts may participate in intratumoral E2 deposition; therefore promoting breast cancer cell growth.
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http://dx.doi.org/10.1016/j.mce.2015.05.032 | DOI Listing |
J Med Chem
January 2025
State Key Laboratory of Natural Medicines and Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
MTDH-SND1 protein-protein interaction (PPI) plays an important role in the initiation and development of tumors, and it is a target for the treatment of breast cancer. In this study, we identified and synthesized a series of novel small-molecule inhibitors of MTDH-SND1 PPI. The representative compound showed potent activity against MTDH-SND1 PPI with an IC of 487 ± 99 nM and tight binding to the SND1-purified protein with a value of 279 ± 17 nM.
View Article and Find Full Text PDFJ Cancer Res Ther
December 2024
School of Chemistry, Chemical Engineering and Life Sciences, Wuhan University of Technology, Wuhan, China.
Tumor-infiltrating lymphocytes (TILs) are key components of the tumor microenvironment (TME) and serve as prognostic markers for breast cancer. Patients with high TIL infiltration generally experience better clinical outcomes and extended survival compared to those with low TIL infiltration. However, as the TME is highly complex and TIL subtypes perform distinct biological functions, TILs may only provide an approximate indication of tumor immune status, potentially leading to biased prognostic results.
View Article and Find Full Text PDFCells
December 2024
Key Laboratory of Marine Drugs (Ministry of Education), Shandong Provincial Key Laboratory of Glycoscience and Glycoengineering, School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, China.
CD24, a highly sialylated glycosyl-phosphatidyl-inositol (GPI) cell surface protein that interacts with sialic acid-binding immunoglobulin-like lectins (Siglecs), serves as an innate immune checkpoint and plays a crucial role in inflammatory diseases and tumor progression. Recently, cytoplasmic CD24 has been observed in samples from patients with cancer. However, whether sialylation governs the subcellular localization of CD24 in cancer remains unclear, and the impact of CD24 expression and localization on the clinical prognosis of cancer remains controversial.
View Article and Find Full Text PDFAsia Pac J Clin Oncol
January 2025
Department of Thyroid and Breast Surgery, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Aim: Breast cancer (BC) is the most frequently diagnosed malignancy worldwide, necessitating continued research into its molecular mechanisms. Circular RNAs (circRNAs) are increasingly recognized for their role in various cancers, including BC. This study explores the role of circRNA kinesin family member 4A (circKIF4A) in BC progression and its underlying molecular mechanisms.
View Article and Find Full Text PDFCureus
December 2024
Pathology, BLDE (Deemed to be University) Shri B M Patil Medical College, Hospital and Research Centre, Vijayapura, IND.
Background Breast carcinoma cases are rising steadily and represent a major cause of mortality and morbidity in India. In response to breast carcinoma, the immune system is activated, resulting in lymphocyte infiltration in and around the tumor nests. This interaction between the tumor and immune system is the basis for studying tumor-infiltrating lymphocytes (TILs).
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