Abstract We have used in vitro and mouse xenograft models to examine the interaction between breast cancer stem cells (CSC) bone marrow–derived mesenchymal (MSC). show that both of these cell populations are organized a cellular hierarchy which primitive aldehyde dehydrogenase expressing regulate CSCs through cytokine loops involving IL6 CXCL7. In NOD/SCID mice, labeled MSCs introduced into tibia traffic sites growing tumor xenografts where they accelerated growth by increasing CSC...

Several reports have recently documented that CXCR7/RDC1 functions as a chemokine receptor for SDF-1/CXCL12, which regulates spectrum of normal and pathological processes. In this study, the role in prostate cancer (PCa) was explored. Staining high density tissue microarrays demonstrates levels expression increase tumors become more aggressive. vitro vivo studies with PCa cell lines suggest alterations are associated enhanced adhesive invasive activities addition to survival advantage....

To delineate the role of SDF-1 and CXCR4 in metastatic prostate cancer (CaP), positive correlations were established between levels tumor metastasis. Neutralization limited number growth intraosseous metastasis vivo. Together, these vivo data provide critical support that SDF-1/CXCR4 plays a skeletal metastasis.Previously we determined stromal-derived factor-1 (SDF-1)/CXCR4 chemokine axis is activated (CaP) to bone. CaP, evaluated variety tissues whether neutralization prevented and/or...

Abstract The generation of an ‘angiogenic switch’ is essential for tumor growth, yet its regulation poorly understood. In this investigation, we explored the linkage between metastasis and angiogenesis through CXCL12/CXCR4 signaling. We found that CXCR4 regulates expression secretion glycolytic enzyme phosphoglycerate kinase 1 (PGK1). Overexpression PGK1 reduced vascular endothelial growth factor interleukin-8 increased angiostatin. At metastatic sites, however, high levels CXCL12 signaling...

Abstract Disseminated prostate cancer (PCa) cells in the marrow survive for years without evidence of proliferation, while maintaining capacity to develop into metastatic lesions. These dormant disseminated tumor (DTCs) may reside close proximity osteoblasts, expressing high levels Axl, one tyrosine kinase receptors growth arrest specific 6 (Gas6). Yet how Axl regulates DTC proliferation remains undefined. Here, we explored impact loss PCa (PC3 and DU145) on induction their dormancy when...

Prostate cancer (PCa) metastasizes selectively to bone through unknown mechanisms. In the current study, we identified exosome-mediated transfer of pyruvate kinase M2 (PKM2) from PCa cells into marrow stromal (BMSCs) as a novel mechanism which primary tumor-derived exosomes promote premetastatic niche formation. We found that PKM2 up-regulates BMSC CXCL12 production in HIF-1α-dependent fashion, subsequently enhances seeding and growth marrow. Furthermore, serum-derived patients with either...

The mechanisms that regulate hematopoietic stem cell (HSC) dormancy and self-renewal are well established largely dependent on signals emanating from the HSC niche. Recently, we found prostate cancer (PCa) cells target niche in mouse bone marrow (BM) during metastasis. Little is known, however, as to how may cells. In this study, investigated effects of TANK binding kinase 1 (TBK1) PCa BM We with osteoblasts induces expression TBK1 PC3 C4-2B. Interestingly, interacts mammalian rapamycin...

The role of erythropoietin (Epo) and Epo/Epo receptor (EpoR) signaling pathways for production red blood cells are well established. However, little is known about Epo/EpoR in non-hematopoietic cells. Recently, we demonstrated that Epo activates JAK/STAT hematopoietic stem (HSCs), leading to the bone morphogenetic protein 2 (BMP2) formation also directly mesenchymal form osteoblasts vitro. In this study, investigated effects mTOR on Epo-mediated osteoblastogenesis osteoclastogenesis. We...

The receptor tyrosine kinase Axl is overexpressed in a variety of cancers and known to play role proliferation invasion. Previous data from our laboratory indicate that its ligand growth arrest-specific 6 (GAS6) may establishing metastatic dormancy the bone marrow microenvironment. In current study, we found highly expressed prostate cancer cell lines PC3 DU145 has negligible levels expression nonmetastatic line LNCaP. Knockdown cells resulted decreased several mesenchymal markers including...

The process of creating flood inundation maps is affected by uncertainties in data, modeling approaches, parameters, and geoprocessing tools. Generalized likelihood uncertainty estimation (GLUE) one the popular techniques used to represent model predictions through Monte Carlo analysis coupled with Bayesian estimation. objectives this study are (1) compare arising from multiple variables mapping using simulations GLUE (2) investigate role subjective selection measure quantifying mapping....

The purpose of this study was to determine the lineage progression human and murine very small embryonic-like (HuVSEL or MuVSEL) cells in vitro vivo. In vitro, HuVSEL MuVSEL differentiated into all three embryonic germ layers. produced robust mineralized tissue origin compared with controls calvarial defects. Immunohistochemistry demonstrated that gave rise neurons, adipocytes, chondrocytes, osteoblasts within were also able differentiate similar lineages. First round serial transplants...

Many prostate cancer (PCa) recurrences are thought to be due reactivation of disseminated tumor cells (DTCs). We previously found a role the TAM family receptor tyrosine kinases TYRO3, AXL, and MERTK in PCa dormancy regulation. However, mechanism contributions individual receptors is largely unknown. Knockdown MERTK, but not AXL or TYRO3 by shRNA induced decreased ratio P-Erk1/2 P-p38, increased expression p27, NR2F1, SOX2, NANOG, higher levels histone H3K9me3 H3K27me3, G1/G0 arrest, all...

Dissemination of cancer stem cells (CSCs) serves as the basis metastasis. Recently, we demonstrated that circulating prostate targets hematopoietic cell (HSCs) 'niche' in marrow during dissemination. Once niche, disseminated tumor (DTCs) may remain dormant for extended periods. As major function HSC niche is to maintain functions, hypothesized regulates CSC activities DTCs. Here show DTCs recovered from were significantly enriched a phenotype. Critically, conversion CSCs regulated by...

Abstract Clinical observations have identified an association between psychologic stress and cancer relapse, suggesting that the sympathetic nervous system/norepinephrine (NE) plays a role in reactivation of dormant disseminated tumor cells (DTC) bone marrow niche. Here, mechanism by which NE regulates prostate DTCs is explored. directly stimulated cell proliferation through β2-adrenergic receptors (ADRB2). also altered niche indirectly downregulating secretion dormancy inducing molecule...

We developed a sensitive real-time polymerase chain reaction (QPCR) assay that allows us to track early lodging/homing events in vivo. used this technology develop metastasis of human prostate cancer (PCa) growth severe combined immunodeficient mice. For purpose, marked PCa cell lines were implanted subcutaneously or the (orthotopically) mice as models primary tumors. Mice then sacrificed at various time points, and distant tissues investigated for presence metastatic cells. At 3 weeks,...

Human very small embryonic-like (hVSEL) cells are a resident population of multipotent stem in the bone marrow involved turnover and regeneration tissues. The levels VSEL blood greatly increased response to injury, they have been shown repair injured Adult hVSEL cells, SSEA-4(+)/CD133(+)/CXCR4(+)/Lin(-)/CD45(-), express pluripotency markers (Oct-4 Nanog) may be able differentiate into from all 3 germ lineages. isolated by apheresis following granulocyte-colony-stimulating factor mobilization...

The ideally engineered bone should have similar structural and functional properties to the native tissue. Although integrity is critical for regeneration, we know less about modulating of elicited by morphogenetic protein (BMP) than efficacy safety. Erythropoietin (Epo), a primary erythropoietic hormone, has been used augment blood transfusion in orthopedic surgery. However, effects Epo on regeneration are not well known. Here, determined role BMP2-induced using cranial defect model....

Bone is the preferred metastasis site of advanced prostate cancer (PCa). Using an in vivo murine model human PCa cell to bone, we noted that majority animals develop skeletal have either spinal lesions or bones hindlimb. Much less frequently, forelimb. We therefore speculated whether environment forelimb not permissive for growth PCa. Consequently, data on tumor prevalence were normalized account number cells arriving after intravascular injection, marrow cellularity, and hematopoietic stem...

There is evidence that cancer stem-like cells (CSC) and neuroendocrine behavior play critical roles in the pathogenesis clinical course of metastatic castration-resistant prostate (m-CRPC). However, there limited mechanistic understanding how CSC phenotypes impact development m-CRPC. In this study, we explored role intracellular chemokine CXCL12γ induction differentiation its on expression was detected small-cell carcinoma tissues circulating tumor from m-CRPC patients displaying an...

Background: The CXC chemokine receptor 4 (CXCR4) and its ligand, stromal cell–derived factor‐1 (SDF‐1α or ligand 12) are involved in the trafficking of leukocytes into out extravascular tissues. purpose this study was to determine whether SDF‐1α secreted by host cells plays a role recruiting inflammatory periodontia during local inflammation. Methods: levels were determined enzyme‐linked immunosorbent assay gingival crevicular fluid (GCF) 24 individuals with periodontitis versus healthy...

Prostate cancer metastases and hematopoietic stem cells (HSC) frequently home to the bone marrow, where they compete occupy same HSC niche. We have also shown that under conditions of stress, HSCs secrete morphogenetic proteins (BMP)-2 BMP-6 drives osteoblastic differentiation from mesenchymal precursors. As it is not known, we examined whether metastatic prostate can alter regulation normal formation by progenitor (HPC). HSC/HPCs isolated mice bearing nonmetastatic tumor were their ability...

A need for more accurate flood inundation maps has recently arisen because of the increasing frequency and extremity events. The accuracy is determined by uncertainty propagated from all variables involved in overall process modelling. Despite our advanced understanding progression, it impossible to eliminate constraints involving cost, time, knowledge, technology. Nevertheless, analysis mapping can provide useful information risk management. twin objectives this study were firstly estimate...

Approximately 80% of prostate cancers exhibit some degree bone metastasis. The role the marrow and hematopoietic stem cell (HSC) niche in attracting metastatic cells maintaining dormancy disseminated tumor (DTCs) is an increasingly important topic towards development novel cancer therapies. This paper reviews aspects HSC that lead to homing marrow. review also discusses DTCs environment erythropoietin targeting within niche.