Macrophages Cytokine Spp1 Increases Growth of Prostate Intraepithelial Neoplasia to Promote Prostate Tumor Progression

Prostate cancer development and progression are associated with increased infiltrating macrophages. Prostate cancer is derived from prostatic intraepithelial neoplasia (PIN) lesions. However, the effects macrophages have on PIN progression remain unclear. Here, we showed that the recruited macrophages adjacent to PIN expressed M2 macrophage markers. In addition, high levels of Spp1 transcripts, also known as osteopontin, were identified in these macrophages. Extraneously added Spp1 accelerated PIN cell proliferation through activation of Akt and JNK in a 3D culture setting. We also showed that PIN cells expressed CD44, integrin alpha v, integrin beta 1, and integrin beta 3, all of which have been previously reported as receptors for Spp1. Finally, blockade of Akt and JNK activation through their specific inhibitor completely abolished macrophage Spp1-induced cell proliferation of PIN. Hence, our data revealed Spp1 as another macrophage cytokine/growth factor and its mediated mechanism to upregulate PIN cell growth, thus promoting prostate cancer development.

Automated summary

This study revealed that recruited macrophages adjacent to prostatic intraepithelial neoplasia (PIN) expressed M2 macrophage markers and high levels of Spp1 transcripts. Extraneously added Spp1 accelerated PIN cell proliferation through activation of Akt and JNK. Furthermore, PIN cells expressed receptors for Spp1, including CD44, integrin alpha v, integrin beta 1, and integrin beta 3. Blockade of Akt and JNK activation completely abolished macrophage Spp1-induced cell proliferation of PIN.