Expression of IGF-IEc Isoform in Renal Cell Carcinoma Tissues

Abstract

Background/Aim: Insulin-like growth factor-I (IGF-I) regulates various aspects of cancer biology. There is a growing body of evidence regarding the potential distinct role of IGF-I isoforms, particularly of IGF-IEc, in the pathophysiology of various human cancer types, however, there are no studies which examined the expression of the different IGF-I isoforms in renal cell carcinoma (RCC). This study aimed to characterize the expression of IGF-IEc in human RCC tissues and investigated whether its expression is associated with the histopathological type of RCC as well as with the overall survival of patients. Materials and Methods: Formalin-fixed paraffin-embedded renal tissue samples from 94 patients (58 males and 36 females) were assessed for IGF-IEc expression by immunohistochemistry. Results: RCC tissues showed mainly cytoplasmic IGF-IEc staining but immunoreactivity of IGF-IEc was also localized in the cell membrane. Significantly lower IGF-IEc expression was found in clear cell RCC vs. all other histological types (p=0.010), and this remained significant after adjusting for tumor size, grade, stage, and mitotic index (p<0.05) . No association was found between IGF-IEc expression level and overall survival of patients with RCC. Conclusion: The differential expression of IGF-IEc isoform among the RCC histopathological types may indicate its histological typespecific regulation and possibly suggests a discrete biological role of this isoform in the pathophysiology of RCC.Renal cell carcinoma (RCC) is the most common kidney malignancy, affecting men more than women, and metastatic disease at presentation occurs in up to one-third of patients. The pathological stage (size of the tumor and the extent of invasion), grade, and histological cell type are widely used in clinical practice for the prognosis of RCC (1). In particular, clear cell is the most common histological type of RCC accounting for 60-70% of cases (2). It represents a genetically and histologically diverse group of cancers that includes chromophobe, papillary, unclassified RCC, and other rare subtypes such as renal medullary carcinoma (3-6).Insulin-like growth factor-I (IGF-I) plays an important role in various aspects of cancer biology, such as cell growth, apoptosis resistance, cell differentiation and migration (7-10) and, thus, it has been implicated in the pathophysiology and prognosis of several human cancer types (11-14), including RCC (2,15,16). IGF-I is not only secreted by the liver, but is also produced by other organs such as skeletal muscle, kidney and brain (17-27). The IGF1 gene consists of six exons and can produce multiple heterogeneous transcripts via alternative splicing during its transcription, namely IGF-IEa, IGF-IEb, and IGF-IEc, which encode the corresponding IGF-I protein isoforms (24,26). Mature IGF-I peptide represents the common bioactive product of all IGF-I isoforms (24, 28) and numerous studies have shown that this peptide is involved in cell survival and protection from apoptosis, as well as in the process of uncontro...

+3179G/A Insulin-Like Growth Factor-1 Receptor Polymorphism: A Novel Susceptibility Contributor in Anti-Ro/SSA Positive Patients with Sjögren’s Syndrome: Potential Clinical and Pathogenetic Implications

“…Given the well-established effects of the IGF1/IGF1R axis in cell growth and survival [37][38][39], we hypothesized that dampened IGF1R expression in SS MSG tissues could be related to apoptotic events in SS salivary gland epithelial cells, as previously described [14]. Towards this end, gene expression of several apoptotic molecules was determined, including caspases 1, 4, and 5, as well as NLRP3-inflammasome components (NLRP3, ASC, IL1β, IL18, IL33).…”

“…Given the well-established effects of the IGF1/IGF1R axis in cell growth and survival [37][38][39], we hypothesized that dampened IGF1R expression in SS MSG tissues could be related to apoptotic events in SS salivary gland epithelial cells, as previously described…”

Salivary Gland Radio-Protection, Regeneration and Repair: Innovative Strategies

“…Growth Factor Therapy-somatomedin C is a hormone, similar to insulin in molecular structure, and actually is better known as IGF-1 or insulin-like growth factor 1 [106]. While a statement as "increased insulin-like growth factor signaling induces cell proliferation, survival and cancer progression" is true, it is traditional and partial, to a great extent.…”