RESUMO
The growth and progression of cancers are crucially regulated by the tumor microenvironment where tumor cells and stromal cells are mutually associated. In this study, we found that stomatin expression was markedly upregulated by the interaction between prostate cancer cells and stromal cells. Stomatin suppressed cancer cell proliferation and enhanced apoptosis in vitro and inhibited xenograft tumor growth in vivo. Stomatin inhibited Akt activation, which is mediated by phosphoinositide-dependent protein kinase 1 (PDPK1). PDPK1 protein stability was maintained by its binding to HSP90. Stomatin interacted with PDPK1 and interfered with the PDPK1-HSP90 complex formation, resulting in decreased PDPK1 expression. Knockdown of stomatin in cancer cells elevated Akt activation and promoted cell increase by promoting the interaction between PDPK1 and HSP90. Clinically, stomatin expression levels were significantly decreased in human prostate cancer samples with high Gleason scores, and lower expression of stomatin was associated with higher recurrence of prostate cancer after the operation. Collectively, these findings demonstrate the tumor-suppressive effect of stromal-induced stomatin on cancer cells. SIGNIFICANCE: These findings reveal that interactions with stromal cells induce expression of stomatin in prostate cancer cells, which suppresses tumor growth via attenuation of the Akt signaling axis.
Assuntos
Proliferação de Células/genética , Proteínas de Membrana/metabolismo , Neoplasias da Próstata/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Proteínas Quinases Dependentes de 3-Fosfoinositídeo/metabolismo , Idoso , Animais , Apoptose/genética , Comunicação Celular , Técnicas de Silenciamento de Genes , Células HEK293 , Células Hep G2 , Humanos , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Neoplasias da Próstata/patologia , Células Estromais/metabolismo , Transfecção , Carga Tumoral/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Early detection and resection of neoplastic lesions are key objectives to diminish colorectal cancer mortality. Resection of superficial colorectal neoplasms, cold snare polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection have all been developed and used worldwide. The pocket-creation method facilitates the resection of tumors in difficult and routine locations. Early detection is the most important first step to maximize the benefits of recent advancements in endoscopic techniques. However, the detection of small, flat-shaped, or faded color lesions remains difficult. Linked color imaging, a novel multi-light technology, facilitates the recognition of minor differences in tissue by enhancing the color contrast between early colorectal neoplasms and surrounding normal mucosa in a bright field of view. The most striking feature of linked color imaging is its ability to display the color of early neoplastic lesions as distinct from inflammatory changes, both of which have similar “redness” when viewed using white light imaging. To increase the detection rate of neoplasms, linked color imaging should be used from the outset for endoscopic observation. Early detection of superficial colorectal tumors can result in decreased mortality from colorectal cancer and maintain a good quality of life for patients.
Assuntos
Humanos , Colonoscopia , Neoplasias Colorretais , Endoscopia , Métodos , Mortalidade , Mucosa , Qualidade de Vida , Proteínas SNARE , GreveRESUMO
A 62-year-old man with a flat early esophageal cancer was referred for endoscopic treatment. White light imaging revealed a pale red lesion, whereas linked color imaging (LCI) and blue laser imaging (BLI) yielded purple and brown images, respectively. Iodine staining demonstrated a large unstained area with a homogenous but very weak pink-color sign. This area appeared more clearly as purple and green on LCI and BLI, respectively; however, a different colored portion was observed at the 4 o'clock position inside the iodine-unstained area. Histopathology findings of the resected specimen revealed squamous intraepithelial neoplasia at the 4 o'clock position and an esophageal squamous cell carcinoma in the remaining iodine-unstained area. LCI and BLI combined with iodine staining produce characteristic images that overcomes the pink-color sign, reflecting the histological features of a flat esophageal neoplasm. This new method is useful for detailed evaluation of early flat squamous cell neoplasms.
Assuntos
Humanos , Pessoa de Meia-Idade , Carcinoma de Células Escamosas , Células Epiteliais , Neoplasias Esofágicas , Iodo , Métodos , Neoplasias de Células EscamosasRESUMO
White light imaging (WLI) may not reveal early upper gastrointestinal cancers. Linked color imaging (LCI) produces bright images in the distant view and is performed for the same screening indications as WLI. LCI and blue laser imaging (BLI) provide excellent visibility of gastric cancers in high color contrast with respect to the surrounding tissue. The characteristic purple and green color of metaplasias on LCI and BLI, respectively, serve to increase the contrast while visualizing gastric cancers regardless of a history of Helicobacter pylori eradication. LCI facilitates color-based recognition of early gastric cancers of all morphological types, including flat lesions or those in an H. pylori-negative normal background mucosa as well as the diagnosis of inflamed mucosae including erosions. LCI reveals changes in mucosal color before the appearance of morphological changes in various gastric lesions. BLI is superior to LCI in the detection of early esophageal cancers and abnormal findings of microstructure and microvasculature in close-up views of upper gastrointestinal cancers. Excellent images can also be obtained with transnasal endoscopy. Using a combination of these modalities allows one to obtain images useful for establishing a diagnosis. It is important to observe esophageal cancers (brown) using BLI and gastric cancers (orange) surrounded by intestinal metaplasia (purple) and duodenal cancers (orange) by LCI.