Blogs for June 2013

The extracellular matrix (ECM) is a well-structured composite of collagens, proteoglycans, glycoproteins, and growth factors proficient of generating variable measures of tissue tensile potency, from mucosal linings to bones. ECM predominantly comprises the cellular milieu outside the circulation and is established as having a major regulatory effect on cell activity.  There has been a considerable amount of attention towards the disparate conditions in which ECM unambiguously sends or alters signals to the surrounding cells. Interactions with ECM influence virtually all features of necessary cellular functions which include proliferation, migration, along with that of protein and gene expression and cell delineation. Specific cell-matrix interactions are critical for the endurance of many cell types, and loss of this adhesion dependence is a classic hallmark of neoplastic change. ECM remodeling promotes tumor...

The Lin28-Let-7 stem cell differentiation regulatory pathway is responsible for maintaining stem cell pluripotency. Specifically, Lin28 causes uridiylation of the let-7 miRNA precursor, which prevents differentiation processing by Dicer. Instead, the Uridylated let-7 is degraded by a previously unidentified exonuclease protein. In the article “A role for the Perlman syndrome exonuclease Dis3l2 in the Lin28-let-7 pathway” HM Chang, et al. used Novus’ Dis3l2 Antibody (NBP1-84740) to identify Dis3l2 as the exonuclease responsible for uridylated let-7 degradation.  Interestingly, Dis3l2 binds several proteins previously implicated in Perlman Sydrome.

The implications of this finding are two-fold: (1) The data suggests that Dis3l2 helps maintain pluripoentcy in stem cells, and (2) although speculative, the Lin28-let-7 pathway may be relevant to Perlman Sydrome and cancer.  Additional research is...

Synaptonemal Complex Protein 1 (SCP1) is a novel tumor antigen that belongs to the growing family of cancer/testis antigens (CTAs). CTAs are theoretically ideal targets for tumor immunotherapy. Unlike most auto-antigens, CTAs are highly immunogenic, even in the autologous cancer-bearing patients. Furthermore, because of their very restricted normal tissue expression, immunotherapy targeting CTAs is expected to be more specific and less toxic. These two theoretical properties of CTAs have arisen from the belief that, because they are testicular-specific, they are normally only expressed in the immune privileged testicles where there is an apparent lack of human leukocyte antigen (HLA) class I molecules on the surface of germ cells (1).

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E-cadherin (also known as Arc-1, uvomorulin, and cell-CAM 120/80) is a calcium-regulated adhesion molecule expressed in most normal epithelial tissues and the loss of E-cadherin can cause dedifferentiation and invasiveness in several cancers (1). Loss of E-Cadherin expression correlated with the invasiveness of carcinoma (2). Carcinoma cell lines with an epithelioid phenotype were noninvasive and expressed E-cadherin suggesting a reciprocal relationship between levels of E-Cadherin expression and their invasiveness as detected by E-Cadherin antibodies (3).

Reduced expression of E-cadherin by IHC has been...

Integrins are a group of trans-membrane receptors which encompass alpha and beta subunits acting as adhesion particles in addition to various other important cellular functions. Integrins are recognized to enable cell-cell, cell-ECM, cell-pathogen interface along with signaling through the plasma membrane comprising of critical cellular functions such as differentiation, migration in addition to survival. Several investigators have documented variations in integrin expression and function in several cancers. Numerous integrins such as αVβ3, αVβ5 and α5β1 are attributed to angiogenesis, a critical factor in tumor metastasis and tumor growth. In a recent study (1) it has been demonstrated that the integrins are capable of regulating the expression and activity of several proteases through various pathways there by contributing to the invasive potential of several tumors. FACS has also...