Blood platelets stimulate cancer extravasation through TGFβ-mediated downregulation of PRH/HHEX

Cancer cells go through a process known as epithelial–mesenchymal transition (EMT) during which they acquire the ability to migrate and invade extracellular matrix. Some cells also acquire the ability to move across a layer of endothelial cells to enter and exit the bloodstream; intra- and extravasation, respectively. The transcription factor PRH/HHEX (proline-rich homeodomain/haematopoietically expressed homeobox) controls cell proliferation and cell migration/invasion in a range of cell types. Our previous work showed that PRH activity is downregulated in prostate cancer cells owing to increased inhibitory PRH phosphorylation and that this increases cell proliferation and invasion. PRH inhibits migration and invasion by prostate and breast epithelial cells in part by activating the transcription of Endoglin, a transforming growth factor β (TGFβ) co-receptor. Here we show that depletion of PRH in immortalised prostate epithelial cells results in increased extravasation in vitro. We show that blood platelets stimulate extravasation of cells with depleted PRH and that inhibition of TGFβ signalling blocks the effects of platelets on these cells. Moreover, TGFβ induces changes characteristic of EMT including decreased E-Cadherin expression and increased Snail expression. We show that in prostate cells PRH regulates multiple genes involved in EMT and TGFβ signalling. However, both platelets and TGFβ increase PRH phosphorylation. In addition, TGFβ increases binding of its effector pSMAD3 to the PRH/HHEX promoter and downregulates PRH protein and mRNA levels. Thus, TGFβ signalling downregulates PRH activity by multiple mechanisms and induces an EMT that facilitates extravasation and sensitises cells to TGFβ

Mucous membrane pemphigoid with exclusive gingival involvement: Report of a case and review of literature

According to Sir William Osler, Mouth is the mirror of the body which reflects systemic -diseases. The oral mucosa may be affected by a variety of mucocutaneous diseases and oral lesions may occur first or very early in several mucocutaneous disorders. The erosive gingival lesions associated with vesiculobullous diseases such as lichen planus, cicatricial pemphigoid, and pemphigus vulgaris have been collectively referred to as "Desquamative gingivitis" (DG). Gingival desquamation is a clinical sign in which the gingiva appears reddish, painful, glazed and friable with destruction of the epithelium. This gingival desquamation is due to various disease processes in gingiva. The disease process may be a localized disease of gingiva or a systemic disease which manifests in the gingiva. It is important to be aware of this rare clinical entity so as to distinguish DG from plaque induced gingivitis which is an extremely common condition, easily recognized and treated daily by the dental surgeon. Accurate diagnosis and effective treatment of these lesions may greatly diminish or reverse disease progression. Here by, we present a case of mucous membrane pemphigoid presenting as gingival desquamation in a 45 year old female. Our patient presented with generalized erythematous gingiva and gingival desquamation involving the free, attached and marginal gingiva of left maxillary and mandibular dentition. However, other mucosal and skin involvement was not appreciated in the present case. Thorough history, clinical examination, histopathology and immunofluorescence studies helped us to arrive at the diagnosis of this rare sub-epithelial blistering disorder

Cancer models in preclinical research: A chronicle review of advancement in effective cancer research

Abstract Cancer is a major stress for public well‐being and is the most dreadful disease. The models used in the discovery of cancer treatment are continuously changing and extending toward advanced preclinical studies. Cancer models are either naturally existing or artificially prepared experimental systems that show similar features with human tumors though the heterogeneous nature of the tumor is very familiar. The choice of the most fitting model to best reflect the given tumor system is one of the real difficulties for cancer examination. Therefore, vast studies have been conducted on the cancer models for developing a better understanding of cancer invasion, progression, and early detection. These models give an insight into cancer etiology, molecular basis, host tumor interaction, the role of microenvironment, and tumor heterogeneity in tumor metastasis. These models are also used to predict novel cancer markers, targeted therapies, and are extremely helpful in drug development. In this review, the potential of cancer models to be used as a platform for drug screening and therapeutic discoveries are highlighted. Although none of the cancer models is regarded as ideal because each is associated with essential caveats that restraint its application yet by bridging the gap between preliminary cancer research and translational medicine. However, they promise a brighter future for cancer treatment