Prostate Cancer and Cannabis:Cause and CURE

Cannabis has been used for thousands of years as a natural remedy for many ailments but only recently has modern science began to recognize the curing power of cannabis.  In 2011 alone there were about 240,890 new cases and about 33,720 deaths from prostate cancer.  Below are studies that show how cannabis can be an effective therapy for prostate cancer.   With more research we can prove that cannabis does have medicinal value and can greatly aid or cure many ailments.  These are published medical studies that I encourage you to research and share your findings with everyone.  Spread the truth!
Information gathered by David Worrell edited by Cherry Girl

Cause:

CXCL12 / CXCR4 / CXCR7 Chemokine Axis And Cancer Progression
‎”CXCL12 / CXCR4 / CXCR7 chemokine axis and cancer progression.” Sun X, Cheng G, Hao M, Zheng J, Zhou X, Zhang J, Taichman RS, Pienta KJ, Wang J. SourceDepartment of Biochemistry and Molecular & Cell Biology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, People’s Republic of China. Erratum in Cancer Metastasis Rev. 2011 Jun;30(2):269-70.

Chemokine Family and Their Cognate Receptors

Abstract
Chemokines, small pro-inflammatory chemoattractant cytokines that bind to specific G-protein-coupled seven-span transmembrane receptors, are major regulators of cell trafficking and adhesion. The chemokine CXCL12 (also called stromal-derived factor-1) is an important α-chemokine that binds primarily to its cognate receptor CXCR4 and thus regulates the trafficking of normal and malignant cells. For many years, it was believed that CXCR4 was the only receptor for CXCL12. Yet, recent work has demonstrated that CXCL12 also binds to another seven-transmembrane span receptor called CXCR7. Our group and others have established critical roles for CXCR4 and CXCR7 on mediating tumor metastasis in several types of cancers, in addition to their contributions as biomarkers of tumor behavior as well as potential therapeutic targets. Here, we review the current concepts regarding the role of CXCL12 / CXCR4 / CXCR7 axis activation, which regulates the pattern of tumor growth and metastatic spread to organs expressing high levels of CXCL12 to develop secondary tumors. We also summarize recent therapeutic approaches to target these receptors and/or their ligands.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3175097/?tool=pubmed 

Schematic representation showing the role of microenvironment in tumor cell CXCR4 receptor activation in both the primary and metastatic sites.

CURE:

Cannabinoid Receptor CB2 Modulates the CXCL12/CXCR4-Mediated Chemotaxis of T Lymphocytes
‎”Cannabinoid receptor CB2 modulates the CXCL12/CXCR4-mediated chemotaxis of T lymphocytes.
Ghosh S, Preet A, Groopman JE, Ganju RK.
SourceDivision of Experimental Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.

Abstract
Cannabinoids have been shown to influence the immune system. However, their immunomodulatory effects have not been extensively studied. In this investigation, we have observed that both primary and Jurkat T cells express a functional cannabinoid receptor 2 (CB(2)). Furthermore, both the synthetic cannabinoids CP55,940 and WIN55,212-2, as well as the CB(2)-selective agonist JWH-015, caused a significant inhibition of the chemokine CXCL12-induced and CXCR4-mediated chemotaxis of Jurkat T cells, as well as their transendothelial migration. Involvement of the CB(2) receptor was further confirmed by partial reversal of the inhibition using the CB(2)-specific antagonist, AM630. Similarly, CP55,940 and JWH-015 inhibited the CXCL12-induced chemotaxis of primary CD4(+) and CD8(+) T lymphocytes. Further investigation of signaling studies to delineate the mechanism of inhibition revealed that cannabinoids enhance CXCL12-induced p44/42 MAP kinase activity. However, enhanced MAP kinase activity was not responsible for the inhibition of chemotaxis. This suggests that cannabinoids differentially regulate CXCR4-mediated migration and MAP kinase activation in T cells. Cannabinoids were also found to downregulate the PMA-enhanced enzyme activity of matrix metalloproteinase-9, which is known to play an important role in transendothelial migration. This study provides novel information regarding cannabinoid modulation of functional effects in T cells.”
http://www.ncbi.nlm.nih.gov/pubmed/16503355

The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in prostate cancer metastasis
“These results suggest prostate cancers may be influenced by the CXCL12:CXCR4 pathway during metastasis. This pathway would provide a novel target for therapeutic intervention.”
‎”The importance of the CXCL12-CXCR4 chemokine ligand-receptor interaction in prostate cancer metastasis.  Arya M, Patel HR, McGurk C, Tatoud R, Klocker H, Masters J, Williamson M.  Source Prostate Cancer Research Centre, Institute of Urology,University College London, UK. manit_arya@hotmail.com

Abstract
AIM: Chemokines or chemotactic cytokines are known to be important in the directional migration or chemotaxis of leucocytes in conditions of homeostasis and in inflammatory or immunological responses. However, the role of chemokines is extending beyond their involvement in mediating leucocyte trafficking with an increasing body of evidence suggesting these proteins are intimately involved in many stages of tumour development and progression. Our aim was to study the role of the CXCL12:CXCR4 chemokine ligand:receptor complex in determining the organ-specific metastasis of prostate cancer. MATERIALS and

METHODS: CXCR4 mRNA expression was determined by RT-PCR in 3 metastatic prostate cancer cell lines DU145, LNCaP and PC3, the primary prostate cancer cell line 1542 CPT3X and the normal prostate epithelial cell lines 1542 NPTX and Pre 2.8. This was followed by Taqman quantitative PCR analysis of CXCR4 mRNA in these cell lines. Flow cytometry analysis was then used to measure the expression of the CXCR4 receptor protein on the cell surface. The influence of the receptor on cell migration was studied using Transwell, Migration Assays. Finally, Taqman quantitative PCR was performed on RNA obtained from laser microdissected fresh primary prostate tumour and benign tissue samples from patients.

RESULTS: In DU145, LNCaP and PC3 CXCR4 mRNA expression was approximately 1000, 400 and 21 times respectively that of 1542 NPTX, Pre 2.8 and 1542 CPT3X. In patient primary tumour samples and patient benign tissue specimens CXCR4 mRNA expression was similar to that of the metastatic cell line DU145. Flow cytometry analysis showed that significantly higher levels of the CXCR4 receptor were present on the cell surface of the 3 metastatic cell lines. Migration studies revealed that chemotaxis of the metastatic cell lines PC3 and DU145 was enhanced by CXCL12 ligand and inhibited by antibody to CXCR4. CXCL12 did not influence the migration of the normal prostate epithelial cell line 1542 NPTX.

CONCLUSIONS: We have demonstrated that human prostate cell lines derived from metastases express functional CXCR4 receptor and that CXCL12 ligand enhances their migratory capabilities. Also, laser microdissected primary patient tumours and patient benign tissue specimens express CXCR4 mRNA at high levels (it is suggested that post-transcriptional modification of the CXCR4 receptor plays a major role in regulating protein expression). These results suggest prostate cancers may be influenced by the CXCL12:CXCR4 pathway during metastasis. This pathway would provide a novel target for therapeutic intervention.”
http://www.ncbi.nlm.nih.gov/pubmed/15844659

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