SiRNA-mediated reduction of alpha-actinin-1 inhibits pressure-induced murine tumor cell wound implantation and enhances tumor-free survival.
نویسندگان
چکیده
Viable cancer cells can commonly be recovered from surgical sites and venous blood during tumor resection. The adhesion of these cells to surrounding tissues may impact patient outcomes. Iatrogenic exposure to increased extracellular pressure modulates integrin binding affinity and stimulates colon cancer cell adhesion in vitro through an alpha-actinin-1-dependent signaling pathway. We hypothesized that preoperative small interfering RNA-mediated silencing of alpha-actinin-1 in tumor tissue could disrupt pressure-stimulated cancer cell adhesion to murine surgical wounds and thereby enhance subsequent tumor-free survival. Reducing alpha-actinin-1 in CT26 murine adenocarcinoma cells blocked cell adhesion to collagen in vitro and similarly inhibited pressure-induced CT26 implantation in murine surgical wounds in vivo. Surgical wound contamination with pressure-activated CT26 cells significantly reduced tumor-free survival compared to contamination with tumor cells maintained under ambient pressure. However, mice treated with pressure-activated CT26 cells preoperatively transfected with alpha-actinin-1-specific small interfering RNA displayed reduced surgical site implantation and increased tumor-free survival compared to mice exposed to pressure-activated cells expressing normal levels of alpha-actinin-1 protein. These results suggest that pressure activation of malignant cells promotes tumor development and impairs tumor-free survival. alpha-Actinin-1 may be an effective therapeutic target to inhibit perioperative pressure-stimulated tumor cell implantation.
منابع مشابه
Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice.
Iatrogenic tumor cell implantation within surgical wounds can compromise curative cancer surgery. Adhesion of cancer cells, in particular colon cancer cells, is stimulated by exposure to increased extracellular pressure through a cytoskeleton-dependent signaling mechanism requiring FAK, Src, Akt, and paxillin. Mechanical stimuli during tumor resection may therefore negatively impact patient out...
متن کاملMatrine inhibits diethylnitrosamine-induced HCC proliferation in rats through inducing apoptosis via p53, Bax-dependent caspase-3 activation pathway and down-regulating MLCK overexpression
The proliferation of hepatocellular carcinoma (HCC) cells is one of the leading causes of liver cancer mortality in humans. The inhibiting effects of matrine on HCC cell proliferation have been studied, but the mechanism of that inhibition has not been fully elucidated. Since, apoptosis plays an important role in HCC cell proliferation. We examined the apoptosis-inducing effect of matrine on tu...
متن کاملMatrine inhibits diethylnitrosamine-induced HCC proliferation in rats through inducing apoptosis via p53, Bax-dependent caspase-3 activation pathway and down-regulating MLCK overexpression
The proliferation of hepatocellular carcinoma (HCC) cells is one of the leading causes of liver cancer mortality in humans. The inhibiting effects of matrine on HCC cell proliferation have been studied, but the mechanism of that inhibition has not been fully elucidated. Since, apoptosis plays an important role in HCC cell proliferation. We examined the apoptosis-inducing effect of matrine on tu...
متن کاملO 24: Functional Role of The K2p Potassium Channel Task-3 in A Syngeneic Murine Glioma Model
To investigate the effects of the two-pore-domain potassium (K2P) channel TASK-3 in a syngeneic murine model for malignant glioma. Malignant or high-grade glioma (WHO grade III and IV) are the most common and most aggressive primary brain tumors in adults. Despite aggressive multimodal therapy, the outcome of patients with malignant glioma remains poor. However, recent phase I and II trials hav...
متن کاملAlpha-actinin-1 phosphorylation modulates pressure-induced colon cancer cell adhesion through regulation of focal adhesion kinase-Src interaction.
Physical forces including pressure, strain, and shear can be converted into intracellular signals that regulate diverse aspects of cell biology. Exposure to increased extracellular pressure stimulates colon cancer cell adhesion by a beta(1)-integrin-dependent mechanism that requires an intact cytoskeleton and activation of focal adhesion kinase (FAK) and Src. alpha-Actinin facilitates focal adh...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Neoplasia
دوره 10 3 شماره
صفحات -
تاریخ انتشار 2008