Knockout of the tetraspanin Cd9 in the TRAMP model of de novo prostate cancer increases spontaneous metastases in an organ‐specific manner

Prostate cancer is an extremely heterogeneous disease; patients that do progress to late‐stage metastatic prostate cancer have limited treatment options, mostly palliative. Molecules involved in the metastatic cascade may prove beneficial in stratifying patients to assign appropriate treatment modalities and may also prove to be therapeutic antimetastatic targets. The tetraspanin group of molecules are integral membrane proteins that associate with motility‐related proteins such as integrins. Clinical studies have mostly shown that reduced expression levels of the tetraspanin CD9 are correlated with tumour progression in a range of cancers. Furthermore, functional studies have shown CD9 to be involved in cell motility and adhesion and that it may influence metastasis. The effects of endogenous CD9 on prostate cancer initiation and progression were analysed by crossing a Cd9−/− (KO) murine model with a model of de novo developing and spontaneously metastasising prostate cancer, namely the transgenic adenocarcinoma of mouse prostate model. Our study demonstrates for the first time that ablation of Cd9 had no detectable effect on de novo primary tumour onset, but did significantly increase metastasis to the liver but not the lungs. What's new? The ability to distinguish between prostate tumors that are more or less likely to spread could facilitate decisions regarding treatment options for patients. A promising marker for such distinction is the tetraspanin protein CD9, which in experimental studies has been linked to metastasis. Here, Cd9 genetic ablation in the well‐characterized transgenic adenocarcinoma of mouse prostate (TRAMP) model reveals an association between loss of Cd9 expression and increased incidence of metastases to the liver but not the lung. In contrast, Cd9 ablation did not affect primary prostate tumor initiation. The findings suggest that Cd9 acts as a suppressor of metastasis.