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Transforming growth factor-beta (TGFβ) signaling in cancer is context dependent and acts either as a tumor suppressor or a tumor promoter. Loss of function mutation in TGFβ type II receptor (TβRII) is a frequent event in oral cavity squamous cell carcinoma (SCC). Recently, heterogeneity of TGFβ response has been described at the leading edge of SCC and this heterogeneity has been shown to influence stem cell renewal and drug resistance. Because exosome transfer from stromal to breast cancer cells regulates therapy resistance pathways we investigated whether exosomes contain components of the TGFβ signaling pathway and whether exosome transfer between stromal fibroblasts and tumor cells can influence TGFβ signaling in SCC. We demonstrate that exosomes purified from stromal fibroblasts isolated from patients with oral SCC contains TβRII. We also demonstrate that transfer of fibroblast exosomes increases TGFβ signaling in SCC keratinocytes devoid of TβRII which remain non-responsive to TGFβ ligand in the absence of exosome transfer. Overall our data show that stromal communication with tumor cells can direct TGFβ signaling in SCC.

Chronic inflammation is proposed to prime the development of prostate cancer. However, the mechanisms of prostate cancer initiation and development are not completely understood. The α(v)β(6) integrin has been shown to play a role in epithelial development, wound healing and some epithelial cancers [1, 2]. Here, we investigate the expression of α(v)β(6) in mouse models of prostatic inflammation and prostate cancer to establish a possible relationship between inflammation of the prostate, α(v)β(6) expression and the progression of prostate cancer. Using immunohistochemical techniques, we show expression of α(v)β(6) in two in vivo mouse models; the Pten(pc)-/- model containing a prostate- specific Pten tumor suppressor deletion that causes cancer, and the prostate ovalbumin-expressing transgenic (POET) inflammation mouse model. We show that the α(v)β(6) integrin is induced in prostate cancer and inflammation in vivo in these two mouse models. α(v)β(6) is expressed in all the mice with cancer in the Pten(pc-/-) model but not in age-matched wild-type mice. In the POET inflammation model, α(v)β(6) is expressed in mice injected with activated T-cells, but in none of the control mice. In the POET model, we also used real time PCR to assess the expression of Transforming Growth Factor Beta 1 (TGFβ1), a factor in inflammation that is activated by α(v)β(6). In conclusion, through in vivo evidence, we conclude that α(v)β(6) integrin may be a crucial link between prostatic inflammation and prostatic adenocarcinoma.

Cancer stem cells (CSCs) play a key role in initiation and development of cancer and are attractive targets for therapy. The identification of CSC surface receptors to be used as therapeutic targets in vivo remains a difficult task. In this study, we assessed the expression pattern of three surface receptors: CD133, Trop-2 and alpha2beta1 integrin in human prostate cancer in order to identify CSC-niches. CD133 was found to be expressed in small clusters of cells localized in focal areas of benign as well as malignant lesions, suggesting that this protein is a bona fide marker of the prostate stem/progenitor compartment. Trop-2 was localized in both basal and luminal layers of benign glands and was highly expressed in malignant lesions. Moreover, isolated cells in benign and malignant areas were found to co-express both CD133 and Trop-2. alpha2beta1 integrin was expressed in the prostatic epithelium as well as in the surrounding stroma, limiting its utility as a marker of CSCs. In summary, we demonstrate that the combination of CD133 and Trop-2 is useful to mark putative CSC-containing compartments in human prostate.

Integrins are cell surface receptors for extracellular matrix proteins and play a key role in cell survival, proliferation, migration and gene expression. Integrin signaling has been shown to be deregulated in several types of cancer, including prostate cancer. This review is focused on integrin signaling pathways known to be deregulated in prostate cancer and known to promote prostate cancer progression.