Understanding the protective mechanisms utilized by metastatic prostate cancer cells in order to avoid attack by complement or other parts of the innate immune system and to affect tumor angiogenesis and metastasis will help us to identify suitable targets for pharmaceutical intervention. We have shown that at least two different complement-attenuating mechanisms are at work in close proximity to prostasomes: transfer of CD59, which inhibits complement at the level of MAC insertion, and phosphorylation of C3 so as to make it resistant to (physiological) activation and thereby regulate complement at the convertase level. In addition, we have shown that both fibrinogen and vitronectin, which play critical roles in cell adhesion, are targets for prostasome-mediated phosphorylation. Given the broad specificity of the various PKs, it is most likely that other relevant substrates such as proteins involved in angiogenesis or different matrix proteins may be found. Finally, we have demonstrated that expression and function of different proteins capable of mediating these effects (CD59 and PKs, particularly PKA) are highly upregulated on prostasomes derived from malignant cell lines as compared to seminal prostasomes, suggesting that the malignant cell-associated prostasomes have a higher potential to interact with neighboring cells.

The fact that substantial differences are found in protein expression profiles between physiological and pathological prostasomes may be relevant in the search for suitable clinical markers to identify patients with primary prostate cancer who are at risk for developing metastases. In addition, possible targets for therapeutic intervention may include GPI-anchored proteins and specific PKs present at high concentrations in close proximity to metastases. If the overexpression of RCAs and PKs on metastatic prostate cancer cells can be controlled or counteracted, these modifications could possibly also be used to potientate other types of immunotherapy.