A 3D adrenocortical carcinoma tumor platform for preclinical modeling of drug response and matrix metalloproteinase activity.

Adrenocortical carcinoma (ACC) has a poor prognosis, and no new drugs have been identified in decades. The absence of drug development can partly be attributed to a lack of preclinical models. Both animal models and 2D cell cultures of ACC fail to accurately mimic the disease, as animal physiology is inherently different than humans, and 2D cultures fail to represent the crucial 3D architecture.

A 3D adrenocortical carcinoma tumor platform for preclinical modeling of drug response and matrix metalloproteinase activity.

Adrenocortical carcinoma (ACC) has a poor prognosis, and no new drugs have been identified in decades. The absence of drug development can partly be attributed to a lack of preclinical models. Both animal models and 2D cell cultures of ACC fail to accurately mimic the disease, as animal physiology is inherently different than humans, and 2D cultures fail to represent the crucial 3D architecture.

Tumor cell-conditioned media drives collagen remodeling via fibroblast and pericyte activation in an premetastatic niche model.

Primary tumors secrete large quantities of cytokines and exosomes into the bloodstream, which are uptaken at downstream sites and induce a pro-fibrotic, pro-inflammatory premetastatic niche. Niche development is associated with later increased metastatic burden, but the cellular and matrix changes in the niche that facilitate metastasis are yet unknown. Furthermore, there is no current standard model to study this phenomenon.

Pten regulates collagen fibrillogenesis by fibroblasts through SPARC.

Collagen deposition contributes to both high mammographic density and breast cancer progression. Low stromal PTEN expression has been observed in as many as half of breast tumors and is associated with increases in collagen deposition, however the mechanism connecting PTEN loss to increased collagen deposition remains unclear. Here, we demonstrate that Pten knockout in fibroblasts using an Fsp-Cre;PtenloxP/loxP mouse model increases collagen fiber number and fiber size within the mammary gland.

Matrix-metalloproteinase expression and gelatinase activity in the avian retina and their influence on Müller glia proliferation.

Gelatinases are a class of matrix metalloproteinases (MMPs) that degrade the extracellular matrix (ECM) to regulate intercellular signaling and cell migration. Gelatinase activity is tightly regulated via proteolytic activation and through the expression of tissue inhibitors of matrix metalloproteinases (TIMPs). Gelatinase activity has been implicated in retinal pathophysiology in different animal models and human disease.

Signaling Mechanisms of Myofibroblastic Activation: Outside-in and Inside-Out.

Myofibroblasts are central mediators of fibrosis. Typically derived from resident fibroblasts, myofibroblasts represent a heterogeneous population of cells that are principally defined by acquired contractile function and high synthetic ability to produce extracellular matrix (ECM). Current literature sheds new light on the critical role of ECM signaling coupled with mechanotransduction in driving myofibroblastic activation.

A crosstalk between TGF-β/Smad3 and Wnt/β-catenin pathways promotes vascular smooth muscle cell proliferation.

Rationale: Endovascular interventions performed for atherosclerotic lesions trigger excessive vascular smooth muscle cell (SMC) proliferation leading to intimal hyperplasia. Our previous studies show that following endovascular injury, elevated TGF-β/Smad3 promotes SMC proliferation and intimal hyperplasia. Furthermore in cultured SMCs, elevated TGF-β/Smad3 increases the expression of several Wnt genes.

A murine model of arterial restenosis: technical aspects of femoral wire injury.

Cardiovascular disease caused by atherosclerosis is the leading cause of death in the developed world. Narrowing of the vessel lumen, due to atherosclerotic plaque development or the rupturing of established plaques, interrupts normal blood flow leading to various morbidities such as myocardial infarction and stroke. In the clinic endovascular procedures such as angioplasty are commonly performed to reopen the lumen.