I've found two groups of articles that state different conclusions.
According to Aggarwal S, Ricklis RM, Williams SA, Denmeade SR, "Comparative study of PSMA expression in the prostate of mouse, dog, monkey, and human," (Prostate. 2006 Jun 15;66(9):903-10), "PSMA is not expressed in any significant amount in the prostates of mouse, beagle dog, or macaque monkeys in this study but is expressed in high levels by human prostate. These non-human species, therefore, are not suitable toxicologic models to assess prostate damage from PSMA-activated intraprostatic prodrug/protoxin therapies."
However, in the more recent article of Schmidt S, Fracasso G, Colombatti M, Naim HY, "Cloning and characterization of canine prostate-specific membrane antigen," (Prostate. 2013 May;73(6):642-50) it's stated that "We demonstrate that canine PSMA reveals similar characteristics to human PSMA rendering this protein useful as a translational model for investigations of prostate cancer as well as a suitable antigen for targeted therapy studies in dogs."
Another recent article below appears to support PSMA as well:
Lisa Y Wu, Jacqueline M Johnson, Jessica K Simmons, Desiree E Mendes, Jonathan J Geruntho, Tiancheng Liu, Wessel P Dirksen, Thomas J Rosol, William C Davis, Clifford E Berkman, "Biochemical characterization of prostate-specific membrane antigen from canine prostate carcinoma cells," (Prostate, 74:451-457 (2014))
So, can somebody clarify if PSMA can be indeed a useful biomarker to target in the PC canine model? Thanks!
PSA in dogs would provide an excellent translational model for targeted therapies for human prostate cancer. Human prostate cancer is currently treated with some measure of success with surgery and/or various modes of radiation. Both therapies have significant local side effects that significantly decrease the QOL of patients. by damge to surrounding tissues, rectum, bladder and sexual functionalities.
PSA as a biomarker in man is confusing and terrifying for patients waiting for the result. PSA is not specufic for cancer and goes up and down like spring weather.
Canine PSA could provide a useful target for trageted therapy such as radiolabeled immunoglobulin labeled therapy. Specific murine monoclonal Ig reactive with canine PSA, painted over frozen or formalin preserved canine prostate cancer containing tissues and stained with regular immunofloresence reagents would tell you whether dogs can be treated with RIT and at the same time provide a good model for selecting less toxic, more effective targeted therapies for human patients with prostate cancer.
Hi Serge,
it definitely looks like it could work.
But you won't know before checking yourself, if nobody else did, yet.
;-)
Hi Klaus,
It appears that some groups have already checked it but the results are at least a bit controversial to me. So, I'm hoping that somebody can help to sort it out:)
My lab has developed 3 canine prostate cancer cell lines (Ace-1, Leo, Probasco (Probasco in press)). All 3 express PSMA as determined by RT-PCR and flourescent ligand binding.
Thomas Rosol
Thomas,
Do you have it published? I've read about Ace-1 and Leo but not Probasco.
Would you be interested to explore in vivo targeting -see below:
https://www.researchgate.net/post/Does_anyone_want_to_collaborate_on_optical_studies_of_prostate_cancer_and_the_use_of_gold_nanoparticles_as_contrast_agents_for_detection_of_PC
Dear Thomas, we would be very interested in these canine cell lines, as we will test our oncolytic virus VSV-GP in canine prostate cancer in the near future and it would be great to see if canine prostate cancer is as susceptible as canine melanoma and glioblastoma, for which we were able to find cell lines- Dorothee von Laer.
Serge, I would also be very much interested in what would be a good marker for canine prostate cancer.
Dorothee,
I'm on the same page with you on the biomarkers:) I really want to push our optical technique to the next level , i.e. in vivo detecting Au NPs that target PSMA in PC canine model is the ultimate goal. Why PSMA? It appears (literature data) that this marker provides the highest number of copies per cell which facilitates in vivo targeting . However, if some other biomarkers would provide similar or even high numbers it can be even better...Regardless of the biomarker type, it's always a giant leap from in vitro to in vivo.
Here is the qRTPCR data from our lab on PSMA expression in our canine cell lines (Ace-1, Leo, Probasco). Note that the negative control was a transitional cell carcinoma from a female dog that had undetectable or very low mRNA for PSMA.
Note that the Ace-1-DKK1 cells are transfected with human DKK-1 and now have very low PSMA expression.
Dorothee,
Please let me know if you would like me to start the MTA process.
We would need a description of the use of the cell lines and your technology transfer contact person and your full contact info. You can send that info to me at [email protected].
Tom
PSA in dogs would provide an excellent translational model for targeted therapies for human prostate cancer. Human prostate cancer is currently treated with some measure of success with surgery and/or various modes of radiation. Both therapies have significant local side effects that significantly decrease the QOL of patients. by damge to surrounding tissues, rectum, bladder and sexual functionalities.
PSA as a biomarker in man is confusing and terrifying for patients waiting for the result. PSA is not specufic for cancer and goes up and down like spring weather.
Canine PSA could provide a useful target for trageted therapy such as radiolabeled immunoglobulin labeled therapy. Specific murine monoclonal Ig reactive with canine PSA, painted over frozen or formalin preserved canine prostate cancer containing tissues and stained with regular immunofloresence reagents would tell you whether dogs can be treated with RIT and at the same time provide a good model for selecting less toxic, more effective targeted therapies for human patients with prostate cancer.
GFP labeled prostate cancer markers: http://www.protean.cz/en/recombinant-proteins/cancer-markers
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