What is the link between Lysophosphatidylinositol (LPI) and cancer proliferation?

Uwe’s answer:

Very interesting inquiries. In fact, I have been trying to get more information myself especially in the context of certain potentially metastasizing cancers (i.e. ovarian, breast, colon). Much is still to be understood. Here is what I am trying to understand along those lines of questions myself and see if it helps get a better understanding yourself. 

Lysophosphatidylinositol (LPI) is a proposed endocannabinoid that binds with GPR55 (55). There is a defined pathway between them. Not all cancer proliferation is LPI linked. And no studies exist to date (at least that I know of) that look at the long-term administration of 55 blockers on our health and well-being. Mg/kg dose ranges of CBD affecting specific effect via 55 are still wanting. 

Both THC (an agonist) and CBD (an antagonist) bind with 55 but they bind with very different potencies. THC seems to activates 55 with a much stronger force. (THC has been measured to bind at 55 with an EC50 of ~8nM while CBD binds at 55 with an EC50 of ~440nM). (You may remember the larger the nM value the weaker the binding). Activation of 55 has been implicated in the proliferation of these cancers and LPI may part of that process.^1,2,3 

Of course, there are a number of studies that demonstrated THC’s apoptotic potential in the case of other cancers. However, for each of these cancers the majority of studies highlight the therapeutic potential of CBD. So, the current evidence-based logic in the potential cannabinoid-based treatments of these cancers seems to dictate a lean in the direction of CBD or CBD abundant cannabis chemotypes. However, there are a number of other pathways THC (and CBD) induces apoptotic effects. If these outweigh the potentially negative effect of 55 remains to be seen. And, for those wishing to employ THC it would still be advisable to dial in a significant amount of CBD to make up for their different force exerted at 55.

Also, I have not seen any particular research on other cannabinoids binding potential to 55. There is however the endocannabinoid anandamide that binds with 55 which opens up a whole new inquiry of questions since CBD blocks the enzyme that breaks down anandamide and thus increasing its bioavailability including its effect on 55.

Modulation of GPR55 may produce analgesia,⁴ anti-inflammatory actions⁵ and may regulate bone cell function.⁶

1. Hofmann NA, Yang J, Trauger SA, Nakayama H, Huang L, Strunk D, Moses MA, Klagsbrun M, Bischoff J, Graier WF. The GPR 55 agonist, L-α-lysophosphatidylinositol, mediates ovarian carcinoma cell-induced angiogenesis. Br J Pharmacol. 2015 Aug;172(16):4107-18.
2. Andradas C, Blasco-Benito S, Castillo-Lluva S, Dillenburg-Pilla P, Diez-Alarcia R, Juanes-García A, García-Taboada E, Hernando-Llorente R, Soriano J, Hamann S, Wenners A, Alkatout I, Klapper W, Rocken C, Bauer M, Arnold N, Quintanilla M, Megías D, Vicente-Manzanares M, Urigüen, L, Gutkind JS, Guzmán M, Pérez-Gómez E, Sánchez C. Activation of the orphan receptor GPR55 by lysophosphatidylinositol promotes metastasis in triple-negative breast cancer. Oncotarget. 2016 Jul 26;7(30):47565-47575.
3. Kargl J, Andersen L, Hasenöhrl C, et al. GPR55 promotes migration and adhesion of colon cancer cells indicating a role in metastasis. Br J Pharmacol. 2015;173(1):142-54.
4. Staton PC, Hatcher JP, Walker DJ, Morrison AD, Shapland EM, Hughes JP, Chong E, Mander PK, Green PJ, Billinton A, Fulleylove M, Lancaster HC, Smith JC, Bailey LT, Wise A, Brown AJ, Richardson JC, Chessell IP (Sep 2008). “The putative cannabinoid receptor GPR55 plays a role in mechanical hyperalgesia associated with inflammatory and neuropathic pain”. Pain. 139 (1): 225–36.
5. Ibid.
6. Whyte LS, Ryberg E, Sims NA, Ridge SA, Mackie K, Greasley PJ, Ross RA, Rogers MJ (Sep 2009). “The putative cannabinoid receptor GPR55 affects osteoclast function in vitro and bone mass in vivo”. Proceedings of the National Academy of Sciences of the United States of America. 106 (38): 16511–6.