Angiopoietin-Like Protein 4 and Insulin-Like Growth Factor-1 Expression in Invasive Breast Carcinoma in Young Women

Biomarker identification is imperative for invasive breast carcinoma, which is more aggressive and associated with higher mortality and worse prognosis in younger patients (<45 years) than in older patients (>50 years). The current study aimed to investigate angiopoietin-like protein 4 (ANGPTL4) and insulin-like growth factor-1 (IGF-1) protein expression in breast tissue from young patients with breast carcinoma. Immunohistochemical staining was applied in formalin-fixed, paraffin-embedded samples of breast carcinoma tissue from young patients aged <45 years at the time of diagnosis. Both proteins were expressed in the majority of cases. The highest frequency of positive ANGPTL4 and IGF-1 expression was observed in the luminal A subtype, whereas the HER2-overexpression subtype exhibited the lowest expression frequency for both proteins. There was no significant association between ANGPTL4 (p = 0.897) and IGF-1 (p = 0.091) expression and molecular subtypes of breast carcinoma. The histological grade was a significant predictor of ANGPTL4 expression (grade 1 vs. grade 3, adjusted odds ratio = 12.39, p = 0.040). Therefore, ANGPTL-4 and IGF-1 expressions are common in young breast carcinoma tissue. There is a potential use of them as biomarkers in breast carcinoma.

Insulin-like Growth Factor-1 Influences Prostate Cancer Cell Growth and Invasion through an Integrin α3, α5, αV, and β1 Dependent Mechanism

Insulin-like growth factor-1 (IGF-1)-related signaling is associated with prostate cancer progression. Links were explored between IGF-1 and expression of integrin adhesion receptors to evaluate relevance for growth and migration. Androgen-resistant PC3 and DU145 and androgen-sensitive LNCaP and VCaP prostate cancer cells were stimulated with IGF-1 and tumor growth (all cell lines), adhesion and chemotaxis (PC3, DU145) were determined. Evaluation of Akt/mTOR-related proteins, focal adhesion kinase (FAK) and integrin α and β subtype expression followed. Akt knock-down was used to investigate its influence on integrin expression, while FAK blockade served to evaluate its influence on mTOR signaling. Integrin knock-down served to investigate its influence on tumor growth and chemotaxis. Stimulation with IGF-1 activated growth in PC3, DU145, and VCaP cells, and altered adhesion and chemotactic properties of DU145 and PC3 cells. This was associated with time-dependent alterations of the integrins α3, α5, αV, and β1, FAK phosphorylation and Akt/mTOR signaling. Integrin blockade or integrin knock-down in DU145 and PC3 cells altered tumor growth, adhesion, and chemotaxis. Akt knock-down (DU145 cells) cancelled the effect of IGF-1 on α3, α5, and αV integrins, whereas FAK blockade cancelled the effect of IGF-1 on mTOR signaling (DU145 cells). Prostate cancer growth and invasion are thus controlled by a fine-tuned network between IGF-1 driven integrin-FAK signaling and the Akt-mTOR pathway. Concerted targeting of integrin subtypes along with Akt-mTOR signaling could, therefore, open options to prevent progressive dissemination of prostate cancer.

The Multiple Faces of the GH/IGF Axis

Over the past two decades, interest in the role of the somatotroph growth hormone/insulin-like growth factor (GH/IGF1) axis in multiple aspects of physiology and pathology has grown exponentially [...]

Nanoengineered myogenic scaffolds for skeletal muscle tissue engineering

Here, we developed a nano-engineered biomaterial optimized for skeletal muscle proliferation and differentiation. Nanoclay disks were used to control the release of insulin-like growth factor (IGF-1), a key myogenic and immunogenic regulator.