Secreted Protein Acidic and Rich in Cysteine (SPARC) Mediates Metastatic Dormancy of Prostate Cancer in Bone

Sharma, Sambad; Xing, Fei; Yin, Lifang; Wu, Kerui; Said, Neveen; Pochampally, Radhika; Shiozawa, Yusuke; Lin, Hui-Kuan; Balaji, K.C.; Watabe, Kounosuke

doi:10.1074/jbc.m116.737379

Cited by 93 publications

(79 citation statements)

References 69 publications

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“…Indeed, other groups who have derived dormant and tumorigenic cancer cell lines have observed similar growth in culture(Bragado, Estrada et al 2013, Sharma, Xing et al 2016). In agreement with these expectations, we saw no difference in subcutaneous growth in vivo between control and shMER PC3 cells and saw slightly higher growth of Du145 shMER cells compared to control (figure 5A).…”

Section: Resultsmentioning

confidence: 88%

Mer Tyrosine Kinase Regulates Disseminated Prostate Cancer Cellular Dormancy

Cackowski

Eber

Rhee

et al. 2016

J of Cellular Biochemistry

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Many prostate cancer (PCa) recurrences are thought to be due to reactivation of disseminated tumor cells (DTCs). We previously found a role of the TAM family of receptor tyrosine kinases TYRO3, AXL and MERTK in PCa dormancy regulation. However, the mechanism and contributions of the individual TAM receptors is largely unknown. Knockdown of MERTK, but not AXL or TYRO3 by shRNA in PCa cells induced a decreased ratio of P-Erk1/2 to P-p38, increased expression of p27, NR2F1, SOX2, and NANOG, induced higher levels of histone H3K9me3 and H3K27me3, and induced a G1/G0 arrest, all of which are associated with dormancy. Similar effects were also observed with siRNA. Most importantly, knock down of MERTK in PCa cells increased metastasis free survival in an intra-cardiac injection mouse xenograft model. MERTK knockdown also failed to inhibit PCa growth in vitro and subcutaneous growth in vivo, which suggests that MERTK has specificity for dormancy regulation or requires a signal from the PCa microenvironment. The effects of MERTK on the cell cycle and histone methylation were reversed by p38 inhibitor SB203580, which indicates the importance of MAP kinases for MERTK dormancy regulation. Overall, this study shows that MERTK stimulates prostate cancer dormancy escape through a MAP kinase dependent mechanism, also involving p27, pluripotency transcription factors, and histone methylation.

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Section: Resultsmentioning

confidence: 88%

Mer Tyrosine Kinase Regulates Disseminated Prostate Cancer Cellular Dormancy

Cackowski

Eber

Rhee

et al. 2016

J of Cellular Biochemistry

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“…This signalling pathway is well characterised in bone formation [74]. Recently, indolent prostate cancer cells have been reported to secrete SPARC, which can induce BMP7 secretion by bone marrow stromal cells [50], further supporting the role of BMP7 in inducing prostate cancer stem cell senescence [49]. …”

Section: The Fate Of Dtcs In the Bone Marrowmentioning

confidence: 99%

Cancer Cell Colonisation in the Bone Microenvironment

Kan

Vargas

Pape

et al. 2016

IJMS

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Bone metastases are a common complication of epithelial cancers, of which breast, prostate and lung carcinomas are the most common. The establishment of cancer cells to distant sites such as the bone microenvironment requires multiple steps. Tumour cells can acquire properties to allow epithelial-to-mesenchymal transition, extravasation and migration. Within the bone metastatic niche, disseminated tumour cells may enter a dormancy stage or proliferate to adapt and survive, interacting with bone cells such as hematopoietic stem cells, osteoblasts and osteoclasts. Cross-talk with the bone may alter tumour cell properties and, conversely, tumour cells may also acquire characteristics of the surrounding microenvironment, in a process known as osteomimicry. Alternatively, these cells may also express osteomimetic genes that allow cell survival or favour seeding to the bone marrow. The seeding of tumour cells in the bone disrupts bone-forming and bone-resorbing activities, which can lead to macrometastasis in bone. At present, bone macrometastases are incurable with only palliative treatment available. A better understanding of how these processes influence the early onset of bone metastasis may give insight into potential therapies. This review will focus on the early steps of bone colonisation, once disseminated tumour cells enter the bone marrow.

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“…TME has a significant role in the development and metastasis of cancer cells (27, 147, 148). In general, TME is composed of extracellular matrix, fibroblasts, adipocyte, blood vessels, lymphatic vascular networks, and other associated tissue cells (147, 149).…”

Section: Roles Of Evs In Cancer Progressionmentioning

confidence: 99%

Extracellular vesicles as emerging targets in cancer: Recent development from bench to bedside

Xing

et al. 2017

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer

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126

115

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Extracellular vesicles (EVs) have emerged as important players of cancer initiation and progression through cell-cell communication. They have been recognized as critical mediators of extracellular communications, which promote transformation, growth invasion, and drug-resistance of cancer cells. Interestingly, the secretion and uptake of EVs are regulated in a more controlled manner than previously anticipated. EVs are classified into three groups, (i) exosomes, (ii) microvesicles (MVs), and (iii) apoptotic bodies (ABs), based on their sizes and origins, and novel technologies to isolate and distinguish these EVs are evolving. The biologically functional molecules harbored in these EVs, including nucleic acids, lipids, and proteins, have been shown to induce key signaling pathways in both tumor and tumor microenvironment (TME) cells for exacerbating tumor development. While tumor cell-derived EVs are capable of reprogramming stromal cells to generate a proper tumor cell niche, stromal-derived EVs profoundly affect the growth, resistance, and stem cell properties of tumor cells. This review summarizes and discusses these reciprocal communications through EVs in different types of cancers. Further understanding of the patcment of tumor specific therapeutics. This review will also discuss the translational aspects of EVs and therapeutic opportunities of utilizing EVs in different cancer types.

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Secreted Protein Acidic and Rich in Cysteine (SPARC) Mediates Metastatic Dormancy of Prostate Cancer in Bone

Cited by 93 publications

References 69 publications

Mer Tyrosine Kinase Regulates Disseminated Prostate Cancer Cellular Dormancy

Mer Tyrosine Kinase Regulates Disseminated Prostate Cancer Cellular Dormancy

Cancer Cell Colonisation in the Bone Microenvironment

Extracellular vesicles as emerging targets in cancer: Recent development from bench to bedside

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