Cancer‐bone microenvironmental interactions promotes STAT3 signaling
| Autor: | Taaliah Campbell, Jodi Dougan, Valerie Odero-Marah, Simone M. Howard, Liza J. Burton, Kennedi Trice, Veronica Henderson, Ohuod Hawsawi |
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| Rok vydání: | 2019 |
| Předmět: |
Male
STAT3 Transcription Factor 0301 basic medicine Cancer Research Pyridines Cathepsin L Mice Nude chemistry.chemical_element Bone Neoplasms Biology Calcium Bone and Bones Article Mice 03 medical and health sciences chemistry.chemical_compound Paracrine signalling 0302 clinical medicine Cell Movement Cell Line Tumor LNCaP Tumor Microenvironment Animals Humans Phosphorylation RNA Small Interfering Egtazic Acid Molecular Biology Cell Proliferation Mice Inbred BALB C Cell growth Prostatic Neoplasms Cell migration Tyrphostins EGTA Durapatite HEK293 Cells 030104 developmental biology chemistry Cell culture 030220 oncology & carcinogenesis Cancer cell Cancer research RNA Interference Snail Family Transcription Factors Signal Transduction |
| Zdroj: | Mol Carcinog |
| ISSN: | 1098-2744 0899-1987 |
| DOI: | 10.1002/mc.23019 |
| Popis: | Prostate cancer (PCa) patients' mortality is mainly attributed to complications caused by metastasis of the tumor cells to organs critical for survival, such as bone. We hypothesized that PCa cell-bone interactions would promote paracrine signaling. A panel of PCa cell lines were cocultured with hydroxyapatite ([HA]; inorganic component of bone) of different densities. Conditioned media (CM) was collected and analyzed for calcium levels and effect on paracrine signaling, cell migration, and viability in vitro and in vivo. Our results showed that calcium levels were elevated in CM from cancer cell-bone cocultures, compared to media or cancer cells alone, and this could be antagonized by ethylene glycol-bis(2-aminoethyl ether)N,N,N',N'-tetraacetic acid (EGTA), a calcium chelator, or knockdown of Snail protein. We also observed increased signal transducer and activator of transcription 3 (STAT3) phosphorylation and paracrine cell proliferation and migration in LNCaP cells incubated with CM from various cell lines; this phosphorylation and cell migration could be antagonized by Snail knockdown or various inhibitors including EGTA, STAT3 inhibitor (WP1066) or cathepsin L inhibitor (Z-FY-CHO). In vivo, higher HA bone density increased tumorigenicity and migration of tumor cells to HA implant. Our study shows that cancer-bone microenvironment interactions lead to calcium-STAT3 signaling, which may present an area for therapeutic targeting of metastatic PCa. |
| Databáze: | OpenAIRE |
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