The preserved expression of neuropilin (NRP) 1 contributes to a better prognosis in colon cancer.

Vascular endothelial growth factor A (VEGF-A) plays an essential role in tumor progression through stromal neovascularization in malignant solid tumors. Neuropilin (NRP) is considered to be the specific receptor for limited types of VEGF-A isoform, VEGF165. The clinicopathological implications of NRP are not well understood in colon cancer, while almost all colon cancers overexpressed VEGF-A. We examined the expression levels of NRP1 and NRP2 genes in 54 colon cancer cases and paired extraneoplastic tissue with quantitative real-time polymerase chain reaction. The gene expression levels of NRP1 in the tumor (0.431+/-0.583) were significantly decreased compared to those in the extraneoplastic tissue (0.754+/-0.799) (paired t-test, p=0.0208). On the other hand, the gene expression levels of NRP2 in the tumor (0.763+/-0.791) were not decreased compared to those in the extraneoplastic tissue (0.508+/-0.386) (paired t-test, p=0.0511). Twenty cases, with preserved expression of the NRP1 gene in the tumor, showed a better prognosis as compared to the 34 cases with decreased NRP1 expression (p=0.0258, log-rank test). No significant relationship was noted between NRP2 gene expression and prognosis. The results suggested that preserved NRP1 expression provides colon cancer patients with a better prognosis.

A novel variant of cardiac myosin-binding protein-C that is unable to assemble into sarcomeres is expressed in the aged mouse atrium.

Cardiac myosin-binding protein-C (MyBP-C), also known as C-protein, is one of the major myosin-binding proteins localizing at A-bands. MyBP-C has three isoforms encoded by three distinct genes: fast-skeletal, slow-skeletal, and cardiac type. Herein, we are reporting a novel alternative spliced form of cardiac MyBP-C, MyBP-C(+), which includes an extra 30 nucleotides, encoding 10 amino acids in the carboxyl-terminal connectin/titin binding region. This alternative spliced form of MyBP-C(+) has a markedly decreased binding affinity to myosin filaments and connectin/titin in vitro and does not localize to A-bands in cardiac myocytes. When MyBP-C(+) was expressed in chicken cardiac myocytes, sarcomere structure was markedly disorganized, suggesting it has possible dominant negative effects on sarcomere organization. Expression of MyBP-C(+) is hardly detected in ventricles through cardiac development, but its expression gradually increases in atria and becomes the dominant form after 6 mo of age. The present study demonstrates an age-induced new isoform of cardiac MyBP-C harboring possible dominant negative effects on sarcomere assembly.

Neuropilin 1 and neuropilin 2 co-expression is significantly correlated with increased vascularity and poor prognosis in nonsmall cell lung carcinoma.

BACKGROUND: Cell-retained isoforms of vascular endothelial growth factor A (VEGF-A) have been reported to play an essential role in tumor progression through stromal neovascularization in malignant solid tumors. While more than 95% of nonsmall cell lung carcinoma (NSCLC) expresses cell-retained VEGF-A isoform, the clinicopathologic implications of neuropilin (NRP), considered the specific receptor for limited types of VEGF-A isoform, are not well understood. METHODS: The authors examined NRP1 and NRP2 mRNA expression in 68 NSCLCs and 15 extraneoplastic tissues by a densitometry-assisted, semi-quantitative reverse transcription-polymerase chain reaction. The authors determined the distinct expression of NRPs using the expression level of NRPs relative by optical density to beta2-microglobulin. The authors also investigated VEGF-A isoforms, their receptors, and the clinical implications. Vascularity of NSCLC was morphologically estimated on sections immunostained with anti-CD34 antibody. RESULTS: Eleven of 15 extraneoplastic specimens showed NRP1 expression (73.3%) and 8 showed NRP2 expression (53.3%). The expression level of NRP1 or NRP2 of neoplasmic tissue was higher than that of extraneoplastic tissues (P < 0.01, Mann-Whitney U test). Fifty-five and 44 NSCLCs expressed NRP1 and NRP2, respectively. Forty patients co-expressing NRP1 and NRP2 showed significantly poorer prognosis and increased vessel counts as compared to those 28 cases without co-expression (P < 0.05, log-rank test; P < 0.05, Mann-Whitney U test). CONCLUSIONS: The co-expression of NRP1 and NRP2 genes is significantly correlated with tumor progression through neovascularization in NSCLC. These results suggest that both NRP1 and NRP2 are key molecules for stromal vascularization by cell-retained VEGF in NSCLC.

Expression of interleukin-10 is inversely correlated with distant metastasis of renal cell carcinoma.

Interleukin-10 (IL-10) is an immunomodulative cytokine produced by T cells, B cells, and monocytic cells. The significance of IL-10 and IL-10R expression in renal cell carcinoma (RCC) has not been well characterized. In this study, we assessed the correlation between IL-10 gene expression and its pathological significance in 44 RCC specimens. The patients with IL-10 gene expression showed a decreased incidence of metastasis compared to those without IL-10 gene expression. The expression of IL-10 was correlated with vascular endothelial growth factor (VEGF)-A gene expression. These findings suggest that IL-10 gene expression plays some roles in the metastasis of RCC.