Cx43 Present at the Leading Edge Membrane Governs Promigratory Effects of Osteoblast-Conditioned Medium on Human Prostate Cancer Cells in the Context of Bone Metastasis

Boucher, Jonathan; Balandre, Annie-Claire; Debant, Marjolaine; Vix, Justine; Harnois, Thomas; Bourmeyster, Nicolas; Péraudeau, Elodie; Chépied, Amandine; Clarhaut, Jonathan; Debiais, Françoise; Monvoisin, Arnaud; Cronier, Laurent

doi:10.3390/cancers12103013

Cited by 6 publications

(3 citation statements)

References 72 publications

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“…The disruption of homeostasis between osteoblasts is involved in PCa-induced osteogenesis (2,24). These processes are regulated by tumor cell-derived cytokines, such as bone morphogenetic protein, platelet-derived growth factor, insulin-like growth factor and extracellular calcium (25)(26)(27)(28). As an extracellular matrix protein, increased levels of spondin 2 in serum are correlated with high incidence of osteogenesis induced by prostate tumor cells (29).…”

Section: Discussionmentioning

confidence: 99%

Prostate cancer cell‑derived spondin 2 boosts osteogenic factor levels in osteoblasts via the PI3K/AKT/mTOR pathway

Wang

Zhang

et al. 2022

Oncol Rep

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Prostate cancer is the leading cause of cancer death among men worldwide. Bone metastasis is one of the main problems arising from prostate cancer. Spondin 2 is a diagnostic marker specific for prostate cancer; however, the role of spondin 2 in prostate cancer-driven osteogenesis remains unclear. The present study was carried out to explore the role of spondin 2 on prostate cancer cell-induced osteogenesis. In the present study, the expression of spondin 2 was analyzed in prostate cancer samples obtained from Gene Expression Omnibus. The supernatant of prostate cancer cells was used to treat the osteoblast precursor MC3T3-E1 cell line to determine the effect of spondin 2 on osteoblasts. The effect of spondin 2 on osteogenic factor production was also examined after neutralization with a spondin 2 antibody in vitro via reverse transcription-quantitative PCR. Furthermore, the effect of spondin 2 on the PI3K/AKT/mTOR pathway was assessed using a patient dataset from The Cancer Genome Atlas and in vitro via western blot analysis. In addition, an inhibitor of spondin 2 receptor (ATN-161) was used to explore the inhibition effect of spondin 2 receptor in MC3T3-E1 cells. The results showed that spondin 2 promoted Osterix and Runx2 expression in osteoblasts, and this process was tightly associated with the activation of the PI3K/AKT/mTOR pathway. Moreover, it was demonstrated that the function of spondin 2 on prostate cancer-driven osteogenesis at least partly relied on the integrin receptor α5β1. These results demonstrated that spondin 2 boosts osteogenesis via the PI3K/AKT/mTOR pathway under conditions of prostate tumor progression.

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Section: Discussionmentioning

confidence: 99%

Prostate cancer cell‑derived spondin 2 boosts osteogenic factor levels in osteoblasts via the PI3K/AKT/mTOR pathway

Wang

Zhang

et al. 2022

Oncol Rep

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“…Current therapies for prostatic cancer bone metastases continue to focus on reducing symptoms and improving quality of life in these patients. Bone metastases can result in many complications, such as refractory bone pain, hypercalcemia, pathologic fractures, and spinal cord compression, and can even cause more serious complications, such as permanent paralysis ( Boucher et al, 2020 ; Xue et al, 2020 ). Therefore, an effective treatment strategy to reduce the rate of bone metastases and the associated complications is urgently needed in clinical practice to improve patient survival rates and quality of life.…”

Section: Extracellular Vesicles and Bone Metastasismentioning

confidence: 99%

Extracellular Vesicles in Tumors: A Potential Mediator of Bone Metastasis

Wang

2021

Front. Cell Dev. Biol.

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As one of the most common metastatic sites, bone has a unique microenvironment for the growth and prosperity of metastatic tumor cells. Bone metastasis is a common complication for tumor patients and accounts for 15–20% of systemic metastasis, which is only secondary to lung and liver metastasis. Cancers prone to bone metastasis include lung, breast, and prostate cancer. Extracellular vesicles (EVs) are lipid membrane vesicles released from different cell types. It is clear that EVs are associated with multiple biological phenomena and are crucial for intracellular communication by transporting intracellular substances. Recent studies have implicated EVs in the development of cancer. However, the potential roles of EVs in the pathological exchange of bone cells between tumors and the bone microenvironment remain an emerging area. This review is focused on the role of tumor-derived EVs in bone metastasis and possible regulatory mechanisms.

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“…In osteoblast conditioned microenvironment, Cnx43 localized on the membrane mediates tumor cell chemotaxis via its non-channel functions. At the leading edge of migrating cells, Cnx43 C-tail interacts with Rac1 and contractin thus sustaining cell migration towards the osteogenic metastatic niche [117]. The direct interaction of cancer cells with osteoblasts through Cnx43-based gap junctions provides a Ca2+ influx to cancer cells enhancing their malignant potential [118].…”

Section: Connexins As Contributors To Tissue Integrationmentioning

confidence: 99%

The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintaining

Kutova¹,

Pospelov²,

Balalaeva³

2021

Preprint

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The modern paradigm of studying the processes of carcinogenesis and vital activity of tumor tissues implies increased attention to constituents of tumor microenvironment (TME) and their interactions. These interactions between the cells in TME can be mediated via protein junctions of different types. Connexins (Cnxs) are one of the major contributors to intercellular communication. They form gap junctions responsible for the transfer of ions, metabolites, peptides, miRNA, etc. between neighboring tumor cells as well as between tumor and stromal cells. Cnx hemichannels mediate purinergic signaling and bidirectional molecular transport with the extracellular environment. Additionally, Cnxs were reported to localize in tumor-derived exosomes and facilitate the release of their cargo. A large body of evidence implies that the role of connexins in cancer is multifaceted. Pro- or anti-tumorigenic properties of connexins are determined by their abundance, localization and functionality as well as channel assembly and non-channel functions. In this review we have summarized the data on the Cnxs contribution in TME and to the cancer initiation and progression.

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Cx43 Present at the Leading Edge Membrane Governs Promigratory Effects of Osteoblast-Conditioned Medium on Human Prostate Cancer Cells in the Context of Bone Metastasis

Cited by 6 publications

References 72 publications

Prostate cancer cell‑derived spondin 2 boosts osteogenic factor levels in osteoblasts via the PI3K/AKT/mTOR pathway

Prostate cancer cell‑derived spondin 2 boosts osteogenic factor levels in osteoblasts via the PI3K/AKT/mTOR pathway

Extracellular Vesicles in Tumors: A Potential Mediator of Bone Metastasis

The Multifaceted Role of Connexins in Tumor Microenvironment Initiation and Maintaining

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