Extracellular Matrix-Bound FGF2 Mediates Estrogen Receptor Signaling and Therapeutic Response in Breast Cancer.

The extracellular matrix (ECM) is often unaccounted for in studies that consider the stromal contribution to cancer cell signaling and response to treatment. To investigate the influence of a fibrotic microenvironment, we use fibroblast-derived ECM scaffolds as a cell culture platform. We uncover that estrogen receptor-positive (ER) breast cancer cells cultured within ECM-scaffolds have an increase in ER signaling that occurs via an MAPK-dependent, but estrogen-independent manner.

Hypoxia Alters the Response to Anti-EGFR Therapy by Regulating EGFR Expression and Downstream Signaling in a DNA Methylation-Specific and HIF-Dependent Manner.

Intratumoral hypoxia occurs in 90% of solid tumors and is associated with a poor prognosis for patients. Cancer cells respond to hypoxic microenvironments by activating the transcription factors, hypoxia-inducible factor 1 (HIF1) and HIF2. Here, we studied the unique gene expression patterns of 31 different breast cancer cell lines exposed to hypoxic conditions.

RhoB is regulated by hypoxia and modulates metastasis in breast cancer.

Background: RhoB is a Rho family GTPase that is highly homologous to RhoA and RhoC. RhoA and RhoC have been shown to promote tumor progression in many cancer types; however, a distinct role for RhoB in cancer has not been delineated. Additionally, several well-characterized studies have shown that small GTPases such as RhoA, Rac1, and Cdc42 are induced in vitro under hypoxia, but whether and how hypoxia regulates RhoB in breast cancer remains elusive.

Therapeutic Strategies to Block the Hypoxic Response.

Patients with the low levels of O (hypoxia) in their primary tumors have a higher risk for metastasis and death, indicating a need to therapeutically inhibit the effectors of hypoxia. Many strategies have been developed and investigated to block the hypoxic response. For example, inhibitors of HIF-1 and HIF-2 function by altering the transcription, translation, dimerization, nuclear translocation, DNA-binding, or ubiquitination of the HIF proteins.

A software tool for the quantification of metastatic colony growth dynamics and size distributions in vitro and in vivo.

The majority of cancer-related deaths are due to metastasis, hence improved methods to biologically and computationally model metastasis are required. Computational models rely on robust data that is machine-readable. The current methods used to model metastasis in mice involve generating primary tumors by injecting human cells into immune-compromised mice, or by examining genetically engineered mice that are pre-disposed to tumor development and that eventually metastasize.

Molecular Portrait of Hypoxia in Breast Cancer: A Prognostic Signature and Novel HIF-Regulated Genes.

Intratumoral hypoxia has been associated with invasion, metastasis, and treatment failure, prompting the need for a global characterization of the response to hypoxic conditions. The current study presents the results of a large-scale RNA sequencing (RNA-seq) effort, analyzing 31 breast cancer cell lines representative of breast cancer subtypes or normal mammary epithelial (NME) cells exposed to control tissue culture conditions (20% O) or hypoxic conditions (1% O). The results demonstrate that NME have a stronger response to hypoxia both in terms of number of genes induced by hypoxia as well as level of expression.

Tumor Hypoxia As an Enhancer of Inflammation-Mediated Metastasis: Emerging Therapeutic Strategies.

Metastasis is the leading cause of cancer-related deaths. Recent research has implicated tumor inflammation as a promoter of metastasis. Myeloid, lymphoid, and mesenchymal cells in the tumor microenvironment promote inflammatory signaling amongst each other and together with cancer cells to modulate sustained inflammation, which may enhance cancer invasiveness.