Statins affect cancer cell plasticity with distinct consequences for tumor progression and metastasis

Prostate cancer, the second most common malignancy in men, is characterized by high heterogeneity that poses several therapeutic challenges. Epithelial–mesenchymal transition (EMT) is a dynamic, reversible cellular process which is essential in normal embryonic morphogenesis and wound healing. However, the cellular changes that are induced by EMT suggest that it may also play a central role in tumor progression, invasion, metastasis, and resistance to current therapeutic options. These changes include enhanced motility and loss of cell–cell adhesion that form a more aggressive cellular phenotype. Moreover, the reverse process (MET) is a necessary element of the metastatic tumor process. It is highly probable that this cell plasticity reflects a hybrid state between epithelial and mesenchymal status. In this review, we describe the underlying key mechanisms of the EMT-induced phenotype modulation that contribute to prostate tumor aggressiveness and cancer therapy resistance, in an effort to provide a framework of this complex cellular process.

Download Full-text

Review Viruses in cancer cell plasticity: the role of hepatitis C virus in hepatocellular carcinoma

Współczesna Onkologia ◽

10.5114/wo.2014.47132 ◽

2015 ◽

Vol 1A ◽

pp. 62-67

Author(s):

Urszula Hibner ◽

Damien Grégoire

Keyword(s):

Hepatocellular Carcinoma ◽

Hepatitis C Virus ◽

Hepatitis C ◽

Cancer Cell ◽

Cell Plasticity

Download Full-text

Modulation of lung cancer cell plasticity and heterogeneity with the restoration of cisplatin sensitivity by neurotensin antibody

Cancer Letters ◽

10.1016/j.canlet.2018.12.007 ◽

2019 ◽

Vol 444 ◽

pp. 147-161 ◽

Cited By ~ 6

Author(s):

Zherui Wu ◽

Ludovic Fournel ◽

Nicolas Stadler ◽

Jin Liu ◽

Agnès Boullier ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cell ◽

Cell Plasticity ◽

Lung Cancer Cell ◽

Cisplatin Sensitivity

Download Full-text

Interstitial flow promotes macrophage polarization toward an M2 phenotype

Molecular Biology of the Cell ◽

10.1091/mbc.e18-03-0164 ◽

2018 ◽

Vol 29 (16) ◽

pp. 1927-1940 ◽

Cited By ~ 22

Author(s):

Ran Li ◽

Jean Carlos Serrano ◽

Hao Xing ◽

Tara A. Lee ◽

Hesham Azizgolshani ◽

...

Keyword(s):

Fluid Flow ◽

Tumor Microenvironment ◽

Tumor Progression ◽

Cancer Cell ◽

Interstitial Fluid ◽

Macrophage Polarization ◽

Interstitial Flow ◽

Interstitial Fluid Flow ◽

M2 Polarization ◽

Tumor Tissues

Tumor tissues are characterized by an elevated interstitial fluid flow from the tumor to the surrounding stroma. Macrophages in the tumor microenvironment are key contributors to tumor progression. While it is well established that chemical stimuli within the tumor tissues can alter macrophage behaviors, the effects of mechanical stimuli, especially the flow of interstitial fluid in the tumor microenvironment, on macrophage phenotypes have not been explored. Here, we used three-dimensional biomimetic models to reveal that macrophages can sense and respond to pathophysiological levels of interstitial fluid flow reported in tumors (∼3 µm/s). Specifically, interstitial flow (IF) polarizes macrophages toward an M2-like phenotype via integrin/Src-mediated mechanotransduction pathways involving STAT3/6. Consistent with this flow-induced M2 polarization, macrophages treated with IF migrate faster and have an enhanced ability to promote cancer cell migration. Moreover, IF directs macrophages to migrate against the flow. Since IF emanates from the tumor to the surrounding stromal tissues, our results suggest that IF could not only induce M2 polarization of macrophages but also recruit these M2 macrophages toward the tumor masses, contributing to cancer cell invasion and tumor progression. Collectively, our study reveals that IF could be a critical regulator of tumor immune environment.

Download Full-text

Tumor Growth Progression in Ectopic and Orthotopic Xenografts from Inflammatory Breast Cancer Cell Lines

Veterinary Sciences ◽

10.3390/vetsci8090194 ◽

2021 ◽

Vol 8 (9) ◽

pp. 194

Author(s):

Sara Caceres ◽

Angela Alonso-Diez ◽

Belén Crespo ◽

Laura Peña ◽

Maria J. Illera ◽

...

Keyword(s):

Breast Cancer ◽

Tumor Progression ◽

Cell Line ◽

Cancer Cell ◽

Inflammatory Breast Cancer ◽

Steroid Hormone ◽

Cancer Cell Line ◽

Histological Features ◽

Inflammatory Breast Cancer Cell ◽

Orthotopic Xenografts

Xenografts can grow in immunosuppressed hosts, such as SCID mice, and tumor material can be injected into hosts either ectopically or orthotopically. Choosing the correct model to use is a crucial step in animal research. The aim of this study was to report the differences between ectopic and orthotopic xenografts in tumor progression, metastasis capacity, histological features, and steroid hormone profiles in xenografts from the cIMC (canine inflammatory mammary cancer) cell line IPC-366 and hIBC (human inflammatory breast cancer) cell line SUM149. To achieve this purpose, 40 female mice 6–8 weeks old were inoculated with IPC-366 and SUM149 cells subcutaneously (ectopic models) or into mammary fat pad (orthotopic models). Mice were monitored for tumor progression and appearance of metastases, and generated tumors were analyzed in terms of histological examination and steroid hormone production. The results revealed differences in tumor appearance and percentage of metastasis between ectopic and orthotopic models, which were higher in the ectopic xenografts from both cell lines. However, both models had similar characteristics of tumor progression, histological features, and steroid hormone secretion profiles. We show that the ectopic model can be validated as a good and useful model of tumor development in addition to, not contrary to, the orthotopic model in breast cancer research.

Download Full-text

Increased Expression of the Pro-Protein Convertase Furin Predicts Decreased Survival in Ovarian Cancer

Analytical Cellular Pathology ◽

10.1155/2007/930321 ◽

2007 ◽

Vol 29 (4) ◽

pp. 289-299

Author(s):

Robert E. Page ◽

Andrés J. P. Klein-Szanto ◽

Samuel Litwin ◽

Emmanuelle Nicolas ◽

Raid Al-Jumaily ◽

...

Keyword(s):

Ovarian Cancer ◽

Tumor Progression ◽

Real Time ◽

Cell Lines ◽

Cancer Cell ◽

Real Time Pcr ◽

Ovarian Tumor ◽

Cancer Cell Lines ◽

Rt Pcr ◽

Primary Tumors

Background: Proprotein convertases (PCs) are serine proteases that after restricted proteolysis activate many proteins that play a crucial role in cancer such as metalloproteinases, growth factors and growth factor receptors, adhesion molecules, and angiogenic factors. Although the expression of several PCs is increased in many tumors, their expression in primary ovarian tumors has not been studied in detail. We sought to determine if there was an association between the expression of the ubiquitously expressed PCs, furin, PACE-4, PC-5 and PC-7, and ovarian tumor progression. Methods: We assessed their expression by RT-PCR, Real-time PCR, Western blot, and immunohistochemistry using cells derived from normal human ovarian surface epithelium (HOSE) and cancer cell lines as well as ovarian epithelial cancer specimens (45 RT-PCR/Real-time PCR, and 120 archival specimens for Immunohistochemistry). Results: We found that furin expression was restricted to the cancer cell lines. In contrast, PACE-4 and PC-7 showed expression only in normal HOSE cells lines. Furthermore, furin was predominantly expressed in primary tumors from patients who survived for less than five years. The other PCs are either expressed in the group of survivors (PC-7 and PACE4) or expressed in low amounts (PC-5). Conclusions: Our studies point to a clear relationship between furin and ovarian cancer. In addition, these results show that furin exhibits the closest association with ovarian cancer among the ubiquitously expressed PCs, arguing against the redundancy of these proteases. In summary, furin may constitute a marker for ovarian tumor progression and could contribute to predict the outcome of this disease.

Download Full-text