Nonviral CRISPR/Cas9 mutagenesis for streamlined generation of mouse lung cancer models.

Functional analysis in mouse models is necessary to establish the involvement of a set of genetic variations in tumor development. A modeling platform to facilitate and cost-effectively analyze the role of multiple genes in carcinogenesis would be valuable. Here, we present an innovative strategy for lung mutagenesis using CRISPR/Cas9 ribonucleoproteins delivered via cationic polymers.

Low Levels of Amyloid Precursor Protein (APP) Promote Neurogenesis and Decrease Gliogenesis in Human Neural Stem Cells.

Amyloid precursor protein (APP) has been widely studied due to its association with Alzheimer's disease (AD). However, the physiological functions of APP are still largely unexplored. APP is a transmembrane glycoprotein whose expression in humans is abundant in the central nervous system.

Hedgehog Signalling Modulates Immune Response and Protects against Experimental Autoimmune Encephalomyelitis.

The Hedgehog (Hh) pathway is essential for the embryonic development and homeostatic maintenance of many adult tissues and organs. It has also been associated with some functions of the innate and adaptive immune system. However, its involvement in the immune response has not been well determined.

Restrained Th17 response and myeloid cell infiltration into the central nervous system by human decidua-derived mesenchymal stem cells during experimental autoimmune encephalomyelitis.

Background: Multiple sclerosis is a widespread inflammatory demyelinating disease. Several immunomodulatory therapies are available, including interferon-β, glatiramer acetate, natalizumab, fingolimod, and mitoxantrone. Although useful to delay disease progression, they do not provide a definitive cure and are associated with some undesirable side-effects.

NIS mediates iodide uptake in the female reproductive tract and is a poor prognostic factor in ovarian cancer.

Context: The sodium iodide symporter (NIS) mediates active transport of iodide into the thyroid and the lactating mammary glands and is highly expressed in thyroid and breast carcinomas. NIS is clinically very relevant because it allows the treatment with radioiodine of thyroid cancer patients.

Objective: In this study we wanted to explore whether NIS is expressed in the ovary and in ovarian cancer.

Constitutive activation of RANK disrupts mammary cell fate leading to tumorigenesis.

Receptor Activator of NF-kappa B (RANK) pathway controls mammary gland development in mice but its role in mammary stem cell fate remains undefined. We show that constitutive RANK signaling expands luminal and basal mammary compartments including mammary stem and luminal progenitor cell pools and interferes with the generation of CD61+ and Sca1+ luminal cells and Elf5 expression. Impaired mammary cell commitment upon RANK overexpression leads to the accumulation of progenitors including K14+K8+ bipotent cells and the formation of heterogeneous tumors containing hyperplastic basal, luminal, and progenitor cells.

Intraepithelial paracrine Hedgehog signaling induces the expansion of ciliated cells that express diverse progenitor cell markers in the basal epithelium of the mouse mammary gland.

The Hedgehog signaling pathway regulates embryo patterning and progenitor cell homeostasis in adult tissues, including epidermal appendages. A role for the Hh pathway in mammary biology and breast cancer has also been suggested. The aim of this study was to analyze Hh signaling in the mouse mammary gland through the generation of transgenic mice that express Sonic Hedgehog (Shh) under the control of the mammary-specific WAP promoter (WAP-Shh mice).

Hepatocyte growth factor is a lymphangiogenic factor with an indirect mechanism of action.

Hepatocyte growth factor (HGF) has previously been reported to act as a hemangiogenic factor, as well as a mitogenic factor for a variety of tumor cells. Here, we demonstrate that HGF is a lymphangiogenic factor, which may contribute to lymphatic metastasis when overexpressed in tumors. In a mouse corneal lymphangiogenesis model, implantation of HGF induces sprouting and growth of new lymphatic vessel expressing the lymphatic vessel endothelial specific marker hyaluronan receptor-1 (Lyve-1).

Targeted expression of HGF/SF in mouse mammary epithelium leads to metastatic adenosquamous carcinomas through the activation of multiple signal transduction pathways.

Overexpression of hepatocyte growth factor (HGF), also called scatter factor (SF), and its receptor c-Met are associated with poor prognosis for cancer patients. In particular, breast cancer cells can produce HGF that acts in a paracrine as well as in an autocrine manner. Therefore, HGF and c-Met are putative targets for cancer therapy.

Differential requirements for shh in mammary tissue and hair follicle morphogenesis.

Sonic Hedgehog (Shh) is a secreted morphogen that directs patterning and cellular differentiation through binding to its receptor Patched (Ptc). It is required for the development of skin-derived organs, such as hair, whiskers, and teeth. The mammary gland is a skin-derived organ that develops mainly during adult life in which Shh is expressed from puberty to lactation.