Tumor matrix stiffness provides fertile soil for cancer stem cells.

Matrix stiffness is a mechanical characteristic of the extracellular matrix (ECM) that increases from the tumor core to the tumor periphery in a gradient pattern in a variety of solid tumors and can promote proliferation, invasion, metastasis, drug resistance, and recurrence. Cancer stem cells (CSCs) are a rare subpopulation of tumor cells with self-renewal, asymmetric cell division, and differentiation capabilities. CSCs are thought to be responsible for metastasis, tumor recurrence, chemotherapy resistance, and consequently poor clinical outcomes. Evidence suggests that matrix stiffness can activate receptors and mechanosensor/mechanoregulator proteins such as integrin, FAK, and YAP, modulating the characteristics of tumor cells as well as CSCs through different molecular signaling pathways. A deeper understanding of the effect of matrix stiffness on CSCs characteristics could lead to development of innovative cancer therapies. In this review, we discuss how the stiffness of the ECM is sensed by the cells and how the cells respond to this environmental change as well as the effect of matrix stiffness on CSCs characteristics and also the key malignant processes such as proliferation and EMT. Then, we specifically focus on how increased matrix stiffness affects CSCs in breast, lung, liver, pancreatic, and colorectal cancers. We also discuss how the molecules responsible for increased matrix stiffness and the signaling pathways activated by the enhanced stiffness can be manipulated as a therapeutic strategy for cancer.

Periostin: biology and function in cancer.

Periostin (POSTN), a member of the matricellular protein family, is a secreted adhesion-related protein produced in the periosteum and periodontal ligaments. Matricellular proteins are a nonstructural family of extracellular matrix (ECM) proteins that regulate a wide range of biological processes in both normal and pathological conditions. Recent studies have demonstrated the key roles of these ECM proteins in the tumor microenvironment. Furthermore, periostin is an essential regulator of bone and tooth formation and maintenance, as well as cardiac development. Also, periostin interacts with multiple cell-surface receptors, especially integrins, and triggers signals that promote tumor growth. According to recent studies, these signals are implicated in cancer cell survival, epithelial-mesenchymal transition (EMT), invasion, and metastasis. In this review, we will summarize the most current data regarding periostin, its structure and isoforms, expressions, functions, and regulation in normal and cancerous tissues. Emphasis is placed on its association with cancer progression, and also future potential for periostin-targeted therapeutic approaches will be explored.

Overexpression of cytoplasmic dynamin 2 is associated with worse outcomes in patients with clear cell renal cell carcinoma.

BACKGROUND: Dynamin 2 (DNM2) involved in tumor progression in various malignancies. OBJECTIVE: For the first time, we evaluated DNM2 expression pattern, its association with clinicopathological characteristics and survival outcomes in RCC subtypes. METHODS: We evaluated the DNM2 expression pattern in RCC tissues as well as adjacent normal tissue using immunohistochemistry on tissue microarray (TMA) slides. RESULTS: Our findings revealed increased DNM2 expression in RCC samples rather than in adjacent normal tissues. The results indicated that there was a statistically significant difference between cytoplasmic expression of DNM2 among subtypes of RCC in terms of intensity of staining, percentage of positive tumor cells, and H-score (P= 0.024, 0.049, and 0.009, respectively). The analysis revealed that increased cytoplasmic expression of DNM2 in ccRCC is associated with worse OS (log rank: P= 0.045), DSS (P= 0.049), and PFS (P= 0.041). Furthermore, cytoplasmic expression of DNM2 was found as an independent prognostic factor affecting DSS and PFS in multivariate analysis. CONCLUSIONS: Our results indicated that DNM2 cytoplasmic expression is associated with tumor aggressiveness and poor outcomes. DNM2 could serve as a promising prognostic biomarker and therapeutic target in patients with ccRCC.

B Cell Epitopes of Four Fimbriae Antigens of Klebsiella pneumoniae: A Comprehensive In Silico Study for Vaccine Development.

Klebsiella pneumoniae is one of the major causes of nosocomial infections worldwide which can cause several diseases in children and adults. The globally dissemination of hyper-virulent strains of K. pneumoniae and the emergence of antibiotics-resistant isolates of this pathogen narrows down the treatment options and has renewed interest in its vaccines. Vaccine candidates of Klebsiella pneumoniae have not been adequately protective, safe and globally available yet. In K. pneumoniae infection, it is well known that B cells that induce robust humoral immunity are necessary for the host complete protection. Identifying the B cell epitopes of antigens is valuable to design novel vaccine candidates. In the present study using immunoinformatics approaches we found B cell epitopes of four K. pneumoniae type 1 fimbriae antigens namely FimA, FimF, FimG, and FimH. Linear and conformational B cell epitopes of each antigen were predicted using different programs. Subsequently, many bioinformatics assays were applied to choose the best epitopes including prediction antigenicity, toxicity, human similarity and investigation on experimental records. These assays resulted in final four epitopes (each for one Fim protein). These final epitopes were modeled and their physiochemical properties were estimated to be used as potential vaccine candidates. Altogether, we found four B cell epitopes of K. pneumoniae Fim antigens that are immunogen, antigenic, not similar to human peptides, not allergen and not toxic. Also, they have suitable physiochemical properties to administrate as vaccine, although their complete efficacy should be also shown in vitro and in vivo.