Dr. Rolf Brekken : Peregrine Pharmaceuticals KOL :
Spain seems to be a common theme lately...as the Spaniards are dominating this list, but they do seem to welcome Dr. Rolf Brekken and the puzzle pieces continue to build.
SPARC mediates metastatic cooperation between CSC and non-CSC prostate cancer cell subpopulations
Received: 10 February 2014 Accepted: 8 October 2014 Published: 21 October 2014
* Corresponding author: Timothy M Thomson titbmc@ibmb.csic.es
Author Affiliations
1 Department of Cell Biology, Molecular Biology Institute of Barcelona, National Research Council (CSIC), c. Baldiri Reixac 15-21, Barcelona 08028, Spain
2 Networking Research Centre for Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), Instituto de Salud Carlos III, Zaragoza 50018, Spain
3 Functional Validation and Preclinical Research, CIBBIM-Nanomedicine, Vall d’Hebron Research Institute, Barcelona 08035, Spain
4 Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona 08034, Spain
5 Department of Pathology, Hospital Clínic, Barcelona 08034, Spain
6 Biomedical Research and Translational Oncology Unit, Vall d’Hebron Research Institute, Barcelona 08035, Spain
7 Department of Oncology, Hospital Clínic, Barcelona 08034, Spain
8 Laboratory and Department of Urology, Hospital Clínic, Barcelona 08034, Spain
9 Division of Surgical Oncology, Department of Surgery, Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX 75229, USA
10 Universitat de Barcelona, Barcelona 08034, Spain
11 Current address: Department of Molecular Biology, Princeton University, Princeton, NJ 08544-1014, USA
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Molecular Cancer 2014, 13:237 doi:10.1186/1476-4598-13-237
The electronic version of this article is the complete one and can be found online at: www.molecular-cancer.com/content/13/1/237
Results
Comparative secretome analysis yielded 213 proteins differentially secreted between M and S cells. Of these, the protein most abundantly secreted in S relative to M cells was SPARC. Immunodepletion of SPARC inhibited the enhanced invasiveness of M induced by S conditioned medium. Knock down of SPARC in S cells abrogated the capacity of its conditioned medium to enhance the in vitro invasiveness of M cells and compromised their potential to boost the metastatic behavior of M cells in vivo. In most primary human prostate cancer samples, SPARC was expressed in the epithelial tumoral compartment of metastatic cases.
Conclusions
The matricellular protein SPARC, secreted by a prostate cancer clonal tumor cell subpopulation displaying non-CSC properties, is a critical mediator of paracrine effects exerted on a distinct tumor cell subpopulation enriched in CSC. This paracrine interaction results in an enhanced metastatic behavior of the CSC-enriched tumor subpopulation. SPARC is expressed in the neoplastic cells of primary prostate cancer samples from metastatic cases, and could thus constitute a tumor progression biomarker and a therapeutic target in advanced prostate cancer.
I think all those SunRise Phase III sites in "Spain" and all the "Spain" co-authors that are shown here with Dr. Rolf Brekken... are no coincidence at all. Heck... maybe targeting flipped PS helped to understand paracrine cell signaling and with all this new knowledge just may lead to blood tests for many areas. Also, maybe this can help not only stopping bone density loss, but with restoring bone density for healthier teeth. Hopefully we have someone within NIH that will be interested in this.
Think Big... Think Bavi : )
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As any other tissue of the vertebrate and human body, bone is a living tissue that undergoes a continuous remodelling process where the older bone is continuously resorbed by the activity of some cells, the so called “osteoclasts”, and gradually replaced by newly-formed tissue deposited by bone producing cells. “Bone turn-over” is the term which defines this continuous cycle of bone resorption and apposition which is driven by these types of cells. Bone turn-over is finely tuned by biochemical signaling (hormonal, autocrine and paracrine) and is the result of a complex series of biochemical and cellular interactions. These events contradict the apparently inert nature of the bony tissue. Indeed, the annual rate of bone turn-over in a healthy individual ranges from 10% to 20% percent of the whole skeleton [1].
"Bavituximab is a first-in-class phosphatidylserine (PS)-targeting monoclonal antibody that is the cornerstone of a broad clinical pipeline." -- Big Pharmas nightmare... unless they are fortunate enough to have The Bavi Edge!
AI
