Plasma netrin-1 is a diagnostic biomarker of human cancers

I am pleased to report broadening application for our Stem Cell Markers as a diagnostic for cancers. This publication references use of our Netrin-1 antibody.

Ganesan Ramesh, Arthur Berg, and Calpurnia Jayakumar. Plasma netrin-1 is a diagnostic biomarker of human cancers. Biomarkers. Author manuscript; available in PMC 2011 July 26. Published in final edited form as: Biomarkers. 2011 March; 16(2): 172–180. Published online 2011 February 8. doi: 10.3109/1354750X.2010.541564.
Objectives: To determine whether plasma netrin-1 can be used as a diagnostic biomarker of human cancer.

Materials and Methods: A total of 300 cancer plasma samples from breast, renal, prostate, liver, meningioma, pituitary adenoma, glioblastoma, lung, pancreatic and colon cancer patients were compared against 138 control plasma samples. Netrin-1 levels were quantified by ELISA and immunohistochemistry.

Results: Plasma netrin-1 levels were significantly increased in breast, renal, prostate, liver, meningioma, pituitary adenoma, and glioblastoma cancers as compared to control samples.

Discussion and Conclusion: Our results suggest that plasma netrin-1 can be used as a diagnostic biomarker for many human cancers.

Image: Immunohistochemical localization of netrin-1 in renal cell carcinoma (RCC) tissues. A. Secondary antibody control showing no staining. B. Normal adjacent tissues do not show any staining for netrin-1. C. Stage I RCC shows staining for netrin-1. D. Stage II RCC shows staining for netrin-1. E-F.


Netrin-1 Immunohistochemistry: Stage I–III renal cell carcinoma and normal tissue section (Tissue Array) was obtained from Biomax to immunolocalize netrin-1, as described previously (29). Briefly, tissue sections were dewaxed and rehydrated with graded ethanol (100%, 90%, 70% and 30%) and then washed with PBS. Antigen retrieval was carried out using citrate buffer and steamer. The tissue section was permeabilized with 0.2% Triton X-100 in PBS, and washed and blocked with PBS containing 5% donkey serum and 1% BSA. Primary antibodies included a chicken anti-netrin-1 polyclonal antibody (Neuromics cat # CH23002). Primary antibodies were detected using secondary antibodies conjugated with biotin, which was followed by incubation with streptavidin-horseradish peroxidase (Pierce). Slides were mounted in permount and photographed using an Olympus microscope attached to a CCD camera.
Potent diagnostic tools for cancers save lives. This is especially true of markers that can diagnose them in early stages. I will post these important studies as the cross my radar scope.

SOX2 and Initiation of Breast Tumors

I consider it a feather in Neuromics' cap when our reagent(s) are referenced in a Nature Journal. More importantly it enables me to keep the pulse on novel and important discovery.

This pub references use of one of our SOX2 Antibody and comes from Dr. Angel García Martín and his Team at INBIOMED: O Leis, A Eguiara, E Lopez-Arribillaga, M J Alberdi, S Hernandez-Garcia, K Elorriaga, A Pandiella, R Rezola and A G Martin. Sox2 expression in breast tumours and activation in breast cancer stem cells. Oncogene , (8 August 2011) | doi:10.1038/onc.2011.338.

The important insight from this study is: "Over-expression of Sox2 increased mammosphere formation, effect dependent on continuous Sox2 expression; furthermore, Sox2 knockdown prevented mammosphere formation and delayed tumour formation in xenograft tumour initiation models. Induction of Sox2 expression was achieved through activation of the distal enhancer of Sox2 promoter upon sphere formation, the same element that controls Sox2 transcription in pluripotent stem cells. These findings suggest that reactivation of Sox2 represents an early step in breast tumour initiation, explaining tumour heterogeneity by placing the tumour-initiating event in any cell along the axis of mammary differentiation."

Could these findings ultimately lead to a better diagnostic for Breast Cancer? I'll keep you posted.

Lab Highlights: Breast cancer is the most frequent cancer in women making up to 20% of all tumours diagnosed in women, with 1 million new cases diagnosed every year worldwide (16,000 new cases only in Spain). Worlwide it causes over 350,000 deaths with an increasing tendency. Breast cancer stem cells show the phenotype CD44+/CD24low/-Lin- though only a fraction of this population has the capacity to initiate tumours. Therefore a complete and precise description of the breast cancer stem cells is lacking.

The focus of this laboratory is to identify, isolate and culture breast cancer stem cells from natural breast tumours and compare at the molecular level with normal mammary stem cells. This research involves the stablishment of both in vitro and in vivo functional assays and the molecular characterization (both genomic and proteomic) of breast cancer stem cells to define the mechanisms responsible for its transformed phenotype.