Gunnar Ronqvist

Prostasomes – extracellular organelles

We discovered the prostasomes more than 25 years ago and named them. They represented something new with their complex composition and origin from the Golgi apparatus. They appeared membrane-surrounded also in their extracellular context and to realize their presence as organelles extracellularly one has to infer their formation and storage in what we preferred to call "storage vesicles" or multivesicular bodies (MVB) of Golgi origin in their intracellular existence. The MVBs themselves were membrane-surrounded and by a fusion process between these membranes and the plasma membrane of the prostate secretory cell the organelles could be released in toto into the extracellular space. This formation and secretion of prostasomes were not unique events limited to the prostate gland, only, but research by others subsequently revealed similar type of secretion and extracellular occurrence of organelles involving other cell systems as well. The term "exosomes" was coined by R.M. Johnstone 5 years after the corresponding denotation of "prostasomes" in 1982 [1,2].

Physiological and pathophysiological roles of prostasomes

The prostasomes with their complex membrane architecture have been assigned multifunctional features in the normal reproductive process. What is more, evidence has accumulated pointing to a role of prostasomes in the propagation of prostate cancer, based on the findings that also malignant prostate cells are able to produce and export prostasomes to the extracellular environment. Furthermore, the abilities favouring prostate metastatic tumour cell survival and motility in an otherwise hostile environment are upregulated in prostasomes deriving from prostate cancer cells compared to prostasomes from normal secretory prostate cells.

Prostasomes and exosomes are apparently involved in the communication between cells. Exosomes derived from tumour cells may play an important role in the interaction between these cells and their environment; that is, tumour-derived exosomes were shown to be able to transfer tumour antigens to dendritic cells, inducing a CD8+ T-cell-dependent cross-immunization of tumour-bearing mice. These results on native tumour antigens concentrated in exosomes open the possibility of exploiting exosomes as an antigen source in vaccination programs that have already started. We have investigated some critical prostasome-membrane proteins serving as antigens in antiprostasome antibody formation in connection with prostate cancer in man. We are chiselling a strategy in a much alike fashion as that for exosomes to lay the foundations for a vaccination program against prostate cancer in man [3].

References

[1] Ronquist G and Brody I (1985) The prostasome: its secretion and function in man. Biochim Biophys Acta 822, 203–218.

[2] Nilsson BO, Jin M, Einarsson B, Persson BE, Ronquist G (1998) Monoclonal antibodies against human prostasomes. Prostate 35, 178-84.

[3] Ronquist KG, Carlsson L, Ronquist G, Nilsson S, Larsson A (2006) Prostasome-derived proteins capable of eliciting an immune response in prostate cancer patients. Int J Cancer 119, 847-53.