Dynamic bioinspired coculture model for probing ER breast cancer dormancy in the bone marrow niche.

Late recurrences of breast cancer are hypothesized to arise from disseminated tumor cells (DTCs) that reactivate after dormancy and occur most frequently with estrogen receptor-positive (ER) breast cancer cells (BCCs) in bone marrow (BM). Interactions between the BM niche and BCCs are thought to play a pivotal role in recurrence, and relevant model systems are needed for mechanistic insights and improved treatments. We examined dormant DTCs in vivo and observed DTCs near bone lining cells and exhibiting autophagy.

Purinergic Receptor Expression and Cellular Responses to Purinergic Agonists in Human Prostate Cancer Cells.

Background: Anticancer activity of extracellular nucleotides has been investigated in many types of cancer. Herein, the effects of extracellular nucleotides and the receptor profile for these nucleotides on prostate cancer (PCa) were elaborated.

Materials And Methods: PCa cell lines representing different stages of PCa were used.

Identification of Fibulin-1 as a Human Bone Marrow Stromal (HS-5) Cell-Derived Factor That Induces Human Prostate Cancer Cell Death.

Background: Previous studies showed that human bone marrow stromal HS-5 cells secreted unidentified factor(s) inducing PCa cell death. Herein, the HS-5-derived factor (HS-5 DF) was characterized and identified.

Methods: Conditioned media from confluent HS-5 cells were collected and modified for biochemical characteristic testing of HS-5 DF.

Cell-based assays using calcein acetoxymethyl ester show variation in fluorescence with treatment conditions.

The use of fluorogenic compounds in cell and molecular biology has increased in both frequency and range of applications. However, such compounds may introduce artifacts in intracellular fluorescence and cell number estimations as a consequence of interaction with exogenous stimulants, necessitating the use of adequate controls for accurate measurements and valid conclusions. Using calcein acetoxymethyl ester (AM) in combination with various exogenous cellular treatments, we report that the standard practice of direct normalization of experimental values to controls is insufficient for fluorogenic measurements.

Identification of beta-2 as a key cell adhesion molecule in PCa cell neurotropic behavior: a novel ex vivo and biophysical approach.

Prostate cancer (PCa) is believed to metastasize through the blood/lymphatics systems; however, PCa may utilize the extensive innervation of the prostate for glandular egress. The interaction of PCa and its nerve fibers is observed in 80% of PCa and is termed perineural invasion (PNI). PCa cells have been observed traveling through the endoneurium of nerves, although the underlying mechanisms have not been elucidated.

Insidious changes in stromal matrix fuel cancer progression.

Reciprocal interactions between tumor and stromal cells propel cancer progression and metastasis. A complete understanding of the complex contributions of the tumor stroma to cancer progression necessitates a careful examination of the extracellular matrix (ECM), which is largely synthesized and modulated by cancer-associated fibroblasts. This structurally supportive meshwork serves as a signaling scaffold for a myriad of biologic processes and responses favoring tumor progression.

Combination of low dose of genistein and daidzein has synergistic preventive effects on isogenic human prostate cancer cells when compared with individual soy isoflavone.

The reduced incidence of prostate cancer (PCa) in Asia countries has been attributed to high soy diets, and major soy isoflavones, in particular daidzein and genistein, are thought to be the source of the beneficial and anti-cancer effects of soy foods. However, attention has been drawn to the safety of using high levels of soy isoflavones in humans, which is especially the concern for consumers taking regular soy isoflavone dietary supplements. The main objective of this study is thus to identify a soy isoflavone combination with lower levels of daidzein and genistein to be a more efficacious and safer chemo-preventive agent for PCa.

Apoptotic effects of cooked and in vitro digested soy on human prostate cancer cells.

Previous laboratory and animal studies reported that soy isoflavones were major bioactive compounds in soy to exert chemoprotection of prostate cancer. However, these studies cannot reflect the realistic effects that soy may induce through diets, and little is known about the bioavailability of isoflavones from whole soy food and their bioactivities after cooking and digestion. In this study, cooking and in vitro digestion were used to prepare soy extracts and the effects of cooking and digestion on the isoflavone contents and bioactivities of the whole soy extracts were examined.

Differential effects of vitamin D treatment on inflammatory and non-inflammatory breast cancer cell lines.

Vitamin D is a known regulator of breast cancer cell proliferation, apoptosis, migration, invasion and differentiation in vitro. Recent studies have suggested a preventative role for vitamin D in breast cancer development and suggested a possible therapeutic application of vitamin D for patients with various forms of breast cancer. Inflammatory breast cancer (IBC) is a highly aggressive and phenotypically unique form of breast cancer that has a very poor prognosis.

Increased TGF-β1-mediated suppression of growth and motility in castrate-resistant prostate cancer cells is consistent with Smad2/3 signaling.

Background: Elevated TGF-β levels are associated with prostate cancer progression. Although TGF-β is a tumor suppressor for normal epithelial and early-stage cancer cells, it may act paradoxically as a tumor promoter in more advanced cancers, although its effects are largely cell and context dependent. This study analyzed prostate cancer responses to TGF-β signaling in an isogenic model of androgen-sensitive and castration-resistant prostate cancer cells.

Overexpression of the VSSC-associated CAM, β-2, enhances LNCaP cell metastasis associated behavior.

Background: Prostate cancer (PCa) is the second-leading cause of cancer death in American men. This is due largely to the "silent" nature of the disease until it has progressed to a highly metastatic and castrate resistant state. Voltage sensitive sodium channels (VSSCs) are multimeric transmembrane protein complexes comprised of a pore-forming α subunit and one or two β subunits.

Effect of moderate-to-severe chronic kidney disease on flow-mediated dilation and progenitor cells.

A reduction in progenitor cell populations that help preserve vascular continuity and induce vascularization may accentuate endothelial cell apoptosis and dysfunction, ultimately contributing to organ failure and increased cardiovascular disease in chronic kidney disease (CKD). We hypothesized that CD45+ myeloid and CD34+ hematopoietic circulating progenitor cell (CPC) subpopulations would be reduced, peripheral blood mononuclear cell (PBMNC) colony-forming units (CFU) would be impaired, and flow-mediated dilation (FMD) would be impaired in patients with moderate-to-severe CKD as compared with healthy controls. Eleven moderate-to-severe CKD patients (mean estimated glomerular filtration rate [eGFR]: 36 ± 5) and 14 healthy controls were studied; blood was drawn and FMD was assessed by brachial artery FMD.

Paracrine factors produced by bone marrow stromal cells induce apoptosis and neuroendocrine differentiation in prostate cancer cells.

Background: Preferential bony metastasis of human prostate cancer (PCa) cells contributes to disease mortality and morbidity. Local factors in bone stromal extracellular matrix microenvironment affect tumor growth through paracrine interactions between tumor and stromal cells.

Methods: Using co-culture and medium transfer, we used several methods to assess interactions between PCa and bone stromal cells using three PCa cell lines: PC3, LNCaP, and the LNCaP derivative, C4-2B.

Osteoblasts can stimulate prostate cancer growth and transcriptionally down-regulate PSA expression in cell line models.

Introduction: To investigate the effect of bone environment on cellular proliferation, mature prostate-specific antigen (PSA) production and secretion, and PSA transcriptional regulation of prostate cancer cells.

Materials And Methods: Androgen-independent C4-2 prostate cancer cells were co-cultured with various osteoblastic cells in a transwell system. Proliferation was measured via cell counting and MTT assay.

Androgen mediated translational and postranslational regulation of IGFBP-2 in androgen-sensitive LNCaP human prostate cancer cells.

The insulin-like growth factor (IGF) axis is associated intimately with prostate cancer (PCa) development, growth, survival and metastasis. In particular, increased levels of IGFBP-2 expression are associated with advanced PCa, bone metastasis, and the development of castrate resistant PCa. Previously, we reported that androgen treatment decreased intracellular and extracellular IGFBP-2 in the androgen sensitive (AS) PCa cell line, LNCaP.

Short-term intermittent PTH 1-34 administration enhances bone formation in SCID/Beige mice.

The anabolic effect of intermittent PTH on bone is variable depending on the species studied, duration/mode of administration, and location of skeletal response investigated. We tested the hypothesis low dose, short term, intermittent PTH 1-34 administration is sufficient to enhance bone formation without altering bone resorption. To test our hypothesis, mice were treated intermittently with one of three concentrations of PTH 1-34 (1 microg/kg; low, 10 microg/kg, or 20 microg/kg; high) for three weeks.

The developmental expression profile of PAX2 in the murine prostate.

Background: Nine transcription factors comprise the PAX gene family that regulate organogenesis. The urogenital system of PAX2 null male mice fails to develop properly. PAX2 is overexpressed in PC3 cells.

Disease evidence for IGFBP-2 as a key player in prostate cancer progression and development of osteosclerotic lesions.

Accumulating evidence indicates that alterations in the IGF axis contribute to the development of chemo- and radio-resistant, advanced-stage cancers. Additionally, they contribute to hormonal insensitivity in adenocarcinomas such as those derived from prostate and breast. The ligands, IGF-I and IGF-II, along with their receptors, IGF-IR and IGF-IIR, have been implicated in a wide range of disease.

Human prostate fibroblasts induce growth and confer castration resistance and metastatic potential in LNCaP Cells.

Background: The tumor microenvironment is important for progressive and metastatic disease.

Objective: To study the hypothesis that prostate fibroblasts have differential ability to induce castration-resistant prostate cancer (PCa) and metastatic progression and whether this effect might vary depending on the zonal origin of the fibroblast.

Design, Setting, And Participants: Human prostate fibroblasts from the peripheral (PZ), transition (TZ) and central (CZ) zones of radical prostatectomy specimens (n=13) were isolated and compared for their ability to promote androgen independence and metastatic progression in androgen-responsive PCa lymph node carcinoma of the prostate (LNCaP) cells in vivo.

Osteosclerotic prostate cancer metastasis to murine bone are enhanced with increased bone formation.

Spontaneous development of osteoblastic lesions of prostate cancer (PCa) in mice is modeled by orthotopic (intraprostatic) deposition of neoplastic cells followed by an extremely long latency associated with low incidence of spontaneous bone metastasis. Intracardial injection results in overt bone metastases only with osteoclastic PCa cells (i.e.

Quantitative modeling and analysis of the transforming growth factor beta signaling pathway.

Transforming growth factor beta (TGF-beta) signaling, which regulates multiple cellular processes including proliferation, apoptosis, and differentiation, plays an important but incompletely understood role in normal and cancerous tissues. For instance, although TGF-beta functions as a tumor suppressor in the premalignant stages of tumorigenesis, paradoxically, it also seems to act as a tumor promoter in advanced cancer leading to metastasis. The mechanisms by which TGF-beta elicits such diverse responses during cancer progression are still not entirely clear.

Conserved gene expression programs integrate mammalian prostate development and tumorigenesis.

Studies centered at the intersection of embryogenesis and carcinogenesis have identified striking parallels involving signaling pathways that modulate both developmental and neoplastic processes. In the prostate, reciprocal interactions between epithelium and stroma are known to influence neoplasia and also exert morphogenic effects via the urogenital sinus mesenchyme. In this study, we sought to determine molecular relationships between aspects of normal prostate development and prostate carcinogenesis.

Novel surface expression of reticulocalbin 1 on bone endothelial cells and human prostate cancer cells is regulated by TNF-alpha.

An unbiased cDNA expression phage library derived from bone-marrow endothelial cells was used to identify novel surface adhesion molecules that might participate in metastasis. Herein we report that reticulocalbin 1 (RCN1) is a cell surface-associated protein on both endothelial (EC) and prostate cancer (PCa) cell lines. RCN1 is an H/KDEL protein with six EF-hand, calcium-binding motifs, found in the endoplasmic reticulum.

Hormonal regulation of IGFBP-2 proteolysis is attenuated with progression to androgen insensitivity in the LNCaP progression model.

The identification of molecular determinants involved in the promotion of metastasis and development of androgen insensitive prostate cancer (AI-PCa) is necessary to discriminate aggressive from indolent disease and to identify therapeutic targets for advanced disease. Overexpression of one particular member of the insulin like growth factor (IGF) axis, IGFBP-2, is implicated in the development of AI-PCa and other cancers. Using the LNCaP human PCa progression model, we show that the AI and metastatic prostate cancer cell line C4-2B4 expresses greater amounts of secreted IGFBP-2 than the androgen sensitive (AS), non-metastatic LNCaP progenitor cell line.