Carcinosarcomas and Related Cancers: Tumors Caught in the Act of Epithelial-Mesenchymal Transition

2018 ◽  
Vol 36 (2) ◽  
pp. 210-216 ◽  
Author(s):  
Angela Pang ◽  
Mariana Carbini ◽  
Andre L. Moreira ◽  
Robert G. Maki
Keyword(s):  
Clinical Trials ◽  
Phase Transitions ◽  
Epithelial Mesenchymal Transition ◽  
Neuroendocrine Differentiation ◽  
Anatomic Site ◽  
Second Neoplasm ◽  
Mesenchymal Transition ◽  
Reactive Process ◽  
Aggressive Tumors ◽  
Organ Site

In this review, we outline the biology and management of patients with carcinosarcomas and related malignancies, which are often included under the broader concept of sarcomatoid carcinomas. Carcinosarcomas are unusual tumors that are commonly gynecologic in origin, where they are referred to as malignant mixed Müllerian tumors, but may appear in any anatomic site. Although a variety of hypotheses have been presented as to the biphasic nature of these tumors, carcinosarcomas seem to represent the best example in human cancers of the concept of epithelial-mesenchymal transition (EMT), in which the two parts of the tumor are genomically related to one another, as opposed to the mesenchymal component that represents a second neoplasm or (benign) reactive process. In general, patients with carcinosarcomas fare worse than patients with carcinomas of the same anatomic site. Treatment paradigms for carcinosarcomas generally follow those of carcinomas of the same organ site, except where clinical trials provide more specific options. Agents that block or reverse EMT are worth examination in patients with carcinosarcoma and arguably may be even more effective in carcinomas, given evidence of dependence on EMT to generate successful metastases. Information about EMT may also inform other phase transitions in cancer, such as those between prostate or lung carcinoma and more aggressive tumors with neuroendocrine differentiation.

scholarly journals N-cadherin increases after androgen deprivation and is associated with metastasis in prostate cancer

2010 ◽  
Vol 17 (2) ◽  
pp. 469-479 ◽  
Author(s):  
Karin Jennbacken ◽  
Tajana Tešan ◽  
Wanzhong Wang ◽  
Heléne Gustavsson ◽  
Jan-Erik Damber ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Neuroendocrine Differentiation ◽  
Hormonal Treatment ◽  
Androgen Deprivation ◽  
Prostate Tumors ◽  
Primary Tumors ◽  
Mesenchymal Transition ◽  
Molecular Alterations

Androgen-deprivation therapy (ADT) is the standard treatment for metastatic prostate cancer. One factor that has been implicated in the metastatic process is the cell adhesion molecule N-cadherin. In this study, we investigated if the expression of N-cadherin was influenced by androgen deprivation and was associated with metastasis in prostate cancer. The effect of androgen deprivation on N-cadherin expression was initially studied in androgen-dependent (AD) LNCaP and androgen-independent (AI) LNCaP-19 and PC-3 prostate cancer cell lines. Expression of N-cadherin increased in the absence of androgens in AI LNCaP-19 primary tumors and metastases and also in vitro, but not in AI PC-3 tumors, indicating a possible involvement of the androgen receptor in the regulation of N-cadherin. N-cadherin was absent in AD LNCaP tumors. No clear associations between N-cadherin and factors related with epithelial–mesenchymal transition or neuroendocrine differentiation could be established. In addition, N-cadherin was evaluated by immunohistochemistry in human prostate tumors. Expression of N-cadherin was more frequently found in tumors from patients treated with ADT than in tumors from patients with no prior hormonal treatment. N-cadherin expression was also associated with metastasis and Gleason score. Furthermore, increased N-cadherin was detected in prostate cancer biopsies already 3 months after initiation of ADT when tumors were in a regressed state. In summary the results indicate that androgen deprivation induces N-cadherin in prostate tumors. Moreover, N-cadherin was increased in castration-resistant tumors in patients with established metastases. This might indicate that castration induces molecular alterations in the tumor cells, resulting in a more invasive and metastatic phenotype.

scholarly journals The Emerging Role of c-Met in Carcinogenesis and Clinical Implications as a Possible Therapeutic Target

2022 ◽  
Vol 2022 ◽  
pp. 1-12
Author(s):  
Antonio Faiella ◽  
Ferdinando Riccardi ◽  
Giacomo Cartenì ◽  
Martina Chiurazzi ◽  
Livia Onofrio
Keyword(s):  
Clinical Trials ◽  
Epithelial Mesenchymal Transition ◽  
Target Therapy ◽  
Treatment Options ◽  
Survival Rates ◽  
Response To Treatment ◽  
Tyrosine Kinase Receptor ◽  
Mesenchymal Transition ◽  
Surface Receptors ◽  
Clinical Consequences

Background. c-MET is a receptor tyrosine kinase receptor (RTK) for the hepatocyte growth factor (HGF). The binding of HGF to c-MET regulates several cellular functions: differentiation, proliferation, epithelial cell motility, angiogenesis, and epithelial-mesenchymal transition (EMT). Moreover, it is known to be involved in carcinogenesis. Comprehension of HGF-c-MET signaling pathway might have important clinical consequences allowing to predict prognosis, response to treatment, and survival rates based on its expression and dysregulation. Discussion. c-MET represents a useful molecular target for novel engineered drugs. Several clinical trials are underway for various solid tumors and the development of new specific monoclonal antibodies depends on the recent knowledge about the definite c-MET role in each different malignance. Recent clinical trials based on c-MET molecular targets result in good safety profile and represent a promising therapeutic strategy for solid cancers, in monotherapy or in combination with other target drugs. Conclusion. The list of cell surface receptors crosslinking with the c-MET signaling is constantly growing, highlighting the importance of this pathway for personalized target therapy. Research on the combination of c-MET inhibitors with other drugs will hopefully lead to discovery of new effective treatment options.

scholarly journals The paracrine induction of prostate cancer progression by caveolin-1

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Chun-Jung Lin ◽  
Eun-Jin Yun ◽  
U-Ging Lo ◽  
Yu-Ling Tai ◽  
Su Deng ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Stem Cell ◽  
Cancer Progression ◽  
Epithelial Mesenchymal Transition ◽  
Critical Role ◽  
Neuroendocrine Differentiation ◽  
Small Subset ◽  
Castration Resistant Prostate Cancer ◽  
Mesenchymal Transition ◽  
The Impact

Abstract A subpopulation of cancer stem cells (CSCs) plays a critical role of cancer progression, recurrence, and therapeutic resistance. Many studies have indicated that castration-resistant prostate cancer (CRPC) is associated with stem cell phenotypes, which could further promote neuroendocrine transdifferentiation. Although only a small subset of genetically pre-programmed cells in each organ has stem cell capability, CSCs appear to be inducible among a heterogeneous cancer cell population. However, the inductive mechanism(s) leading to the emergence of these CSCs are not fully understood in CRPC. Tumor cells actively produce, release, and utilize exosomes to promote cancer development and metastasis, cancer immune evasion as well as chemotherapeutic resistance; the impact of tumor-derived exosomes (TDE) and its cargo on prostate cancer (PCa) development is still unclear. In this study, we demonstrate that the presence of Cav-1 in TDE acts as a potent driver to induce CSC phenotypes and epithelial–mesenchymal transition in PCa undergoing neuroendocrine differentiation through NFκB signaling pathway. Furthermore, Cav-1 in mCRPC-derived exosomes is capable of inducing radio- and chemo-resistance in recipient cells. Collectively, these data support Cav-1 as a critical driver for mCRPC progression.

Phase transitions in tumor growth VI: Epithelial–Mesenchymal transition

2018 ◽  
Vol 499 ◽  
pp. 208-215 ◽  
Author(s):  
A. Guerra ◽  
D.J. Rodriguez ◽  
S. Montero ◽  
J.A. Betancourt-Mar ◽  
R.R. Martin ◽  
...  
Keyword(s):  
Phase Transitions ◽  
Tumor Growth ◽  
Epithelial Mesenchymal Transition ◽  
Mesenchymal Transition

scholarly journals AKT-induced lncRNA VAL promotes EMT-independent metastasis through diminishing Trim16-dependent Vimentin degradation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Han Tian ◽  
Rong Lian ◽  
Yun Li ◽  
Chenying Liu ◽  
Shujun Liang ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Tumor Invasion ◽  
Tumor Metastasis ◽  
Epithelial Mesenchymal Transition ◽  
Therapeutic Potential ◽  
Anoikis Resistance ◽  
Mesenchymal Transition ◽  
Stat3 Signaling ◽  
Non Coding Rna ◽  
Long Non Coding Rna

Abstract Despite the importance of AKT overactivation in tumor progression, results from clinical trials of various AKT inhibitors remain suboptimal, suggesting that AKT-driven tumor metastasis needs to be further understood. Herein, based on long non-coding RNA (lncRNA) profiling induced by active AKT, we identify that VAL (Vimentin associated lncRNA, LINC01546), which is directly induced by AKT/STAT3 signaling, functions as a potent pro-metastatic molecule and is essential for active AKT-induced tumor invasion, metastasis and anoikis resistance in lung adenocarcinoma (LAD). Impressively, chemosynthetic siRNAs against VAL shows great therapeutic potential in AKT overactivation-driven metastasis. Interestingly, similar to activated AKT in LAD cells, although unable to induce epithelial-mesenchymal transition (EMT), VAL exerts potent pro-invasive and pro-metastatic effects through directly binding to Vimentin and competitively abrogating Trim16-depedent Vimentin polyubiquitination and degradation. Taken together, our study provides an interesting demonstration of a lncRNA-mediated mechanism for active AKT-driven EMT-independent LAD metastasis and indicates the great potential of targeting VAL or Vimentin stability as a therapeutic approach.

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