Defining the populations of tumor-initating cells that are present in tumors is a first step developing therapeutics to target these cells. We show here both CD44(pos)CD24(neg) and CD44(pos)CD24(pos) cell estrogen receptor (ER) alpha-negative breast tumorigenic murine xenograft models. also describe third population xenograft-initiating (XIC) enriched CD44(pos)CD49f(hi)CD133/2(hi) display heightened tumorigenicity, self-renewal vivo, capacity give rise functional molecular heterogeneity....

MicroRNAs (miRNAs) are short endogenous RNAs that regulate multiple biological processes including adipogenesis and fat metabolism. We sought to identify miRNAs correlate with BMI elucidate their upstream regulation downstream targets.Microarray-based expression profiling of 233 was performed on subcutaneous abdominal adipose tissue biopsies from 29 non-diabetic Pima Indian participants. Correlation the levels eight assessed by quantitative reverse transcription (QRT) PCR in samples 80...

The invasive, mesenchymal phenotype of CD44posCD24neg breast cancer cells has made them a promising target for eliminating the metastatic capacity primary tumors. It been previously demonstrated that CD44neg/lowCD24pos lack ability to give rise their invasive counterpart. Here we demonstrate noninvasive, epithelial-like CD44posCD24pos readily progeny in vivo and vitro. This interconversion was found be dependent upon Activin/Nodal signaling.Breast cell lines were sorted into populations...

We examined racial differences in the expression of eight genes and their associations with risk recurrence among 478 white 495 black women who participated Carolina Breast Cancer Study Phase 3. tumor samples were analyzed for PAM50 subtype previously found to be differentially expressed by race associated breast cancer survival: ACOX2, MUC1, FAM177A1, GSTT2, PSPH, PSPHL, SQLE, TYMS. The these according was assessed using linear regression each gene evaluated association Cox regression....

Breast cancer studies implant human cells under the renal capsule, subcutaneously, or orthotopically and often use estrogen supplementation immune suppressants (etoposide) in xenograft mouse models. However, cell behavior is significantly impacted by signals from local microenvironment. Therefore, we investigated how combinatorial effect of location injection procedural differences affected characteristics. Patient-derived breast were injected into abdominal thoracic mammary glands +/-...

Basal-like and luminal breast cancers have distinct stromal–epithelial interactions, which play a role in progression to invasive cancer. However, little is known about how interactions evolve benign pre-invasive lesions. To study epithelial–stromal basal-like cancer progression, we cocultured reduction mammoplasty fibroblasts with the isogenic MCF10 series of cell lines (representing benign/normal, atypical hyperplasia, ductal carcinoma situ). We used gene expression microarrays identify...

Previously, we demonstrated the ability of normal mammary microenvironment (niche) to direct non-mammary cells including testicular and embryonic stem (ESCs) adopt a epithelial cell (MEC) fate. These studies relied upon interaction transplanted MECs with within fat-pads recipient mice that had their endogenous epithelium removed. Here, tested whether acellular extracellular matrix (mECM) preparations are sufficient differentiation testicular-derived ESCs form functional trees in vivo. We...

African American women with breast cancer experience disproportionately poor survival outcomes, primarily due to the high prevalence of deadliest subtype; triple-negative (TNBC). The CRYβB2 gene is upregulated in tumors from patients across all subtypes, including TNBC, and associated worse rates. This study investigated effect on invasion TNBC cells underlying mechanisms contributing this phenotype. We utilized SUM159 stable overexpression a 3D-culture tumor spheroids model our...

Recent evidence suggests an emerging role for S100 protein in breast cancer and tumor progression. These ubiquitous proteins are involved numerous normal pathological cell functions including inflammatory immune responses, Ca(2+) homeostasis, the dynamics of cytoskeleton constituents, as well proliferation, differentiation, death. Our previous proteomic analysis demonstrated presence hornerin, family member, tissue extracellular matrix. Hornerin has been reported healthy skin psoriatic...

The claudin-low molecular subtype of breast cancer is particular interest for clinically the majority these tumors are poor prognosis, triple negative, invasive ductal carcinomas. Claudin-low characterized by stem cell-like features and low expression cell junction adhesion proteins. Herein, we sought to define role lipolysis stimulated lipoprotein receptor (LSR) in behavior as LSR was recently correlated with tumor-initiating features. We show that expressed epithelium, endothelium, stromal...

Elucidating how mitogens facilitate epithelial/stromal interactions is critical given that regulate mammary gland development and function. IGF-I a potent cell mitogen locally produced in the gland. Since IGF-binding proteins (IGFBPs) bioavailability, we characterized cell-type-specific production of IGFBP primary bovine epithelial (BME) fibroblast (BMF) cells. Cells were treated with mRNA levels analyzed via quantitative real-time (qRT)-PCR Northern blot analysis. Media conditioned by cells...

Breast cancer studies frequently focus on the role of tumor microenvironment in promotion cancer; however, influence normal breast cells remains relatively unknown. To investigate cell tumorigenicity, we examined whether extracellular matrix molecules (ECM) derived from premenopausal African-American (AA) or Caucasian-American (CAU) tissue would affect tumorigenicity vitro and vivo. We chose these two populations because well documented predisposition AA women to develop aggressive, highly...

Lipolysis-stimulated lipoprotein receptor (LSR) has been found in the plasma membrane and is believed to function endocytosis tight junctions. Given impact of cellular metabolism junction signaling pathways on tumor phenotypes patient outcome, it important understand how LSR localization mediates its functions. We conducted studies, evaluated DNA binding, examined effects nuclear cells, xenografts, clinical specimens. within membrane, cytoplasm, nucleus breast cancer cells representing...

In this report, we describe a strategy for enhancing the immunogenicity of wide variety Ags by linking them to IL-2 via an IgG3-IL-2 fusion protein with high affinity convenient hapten Ag, dansyl (DNS; N,N-dimethyl-1-aminonaphthalene-5-sulfonyl chloride). This protein, anti-DNS-IgG3-IL-2, combines functional characteristics its constituents and has pharmacokinetic properties that are greatly improved over those previously described IgG1-IL-2 fusion. The molecule is intact recoverable from...

Abstract Background The normal growth and function of mammary epithelial cells depend on interactions with the supportive stroma. Alterations in this communication can lead to progression or expansion malignant growth. human gland contains two distinctive types fibroblasts within are surrounded by loosely connected intralobular fibroblasts, which subsequently more compacted interlobular fibroblasts. different proximity these suggests functions for subtypes. In report, we compared gene...

Macrophages comprise an essential component of the mammary microenvironment necessary for normal gland development. However, there is no viable in vivo model to study their role human breast function. We hypothesized that adding primary macrophages murine would enhance and provide a novel approach examine immune-stromal cell interactions during humanization process.Primary macrophages, presence or absence ectopic estrogen stimulation, were used humanize mouse glands. Mechanisms enhanced...

In the USA, breast cancer mortality rate is 41% higher for African-American women than non-Hispanic White women. While numerous gene expression studies have classified biological features that vary by race and may contribute to poorer outcomes, few experimentally tested these associations. CRYβB2 has drawn particular interest because of its association with overall survival ethnicity in multiple cancers. Several reports indicate overexpression pseudogene, CRYβB2P1, not linked poor outcome....

Translational exploration of bacterial toxins has come to the forefront research given their potential as a chemotherapeutic tool. Studies in select tissues have demonstrated that Clostridium perfringens iota toxin binds CD44 and lipolysis stimulated lipoprotein receptor (LSR) cell-surface proteins. We recently LSR expression correlates with estrogen positive breast cancers signaling directs aggressive, tumor-initiating cell behaviors. Herein, we identify mechanisms cytotoxicity...