scholarly journals The Genomic Processes of Biological Invasions: From Invasive Species to Cancer Metastases and Back Again

2021 ◽  
Vol 9 ◽  
Author(s):  
Fargam Neinavaie ◽  
Arig Ibrahim-Hashim ◽  
Andrew M. Kramer ◽  
Joel S. Brown ◽  
Christina L. Richards
Keyword(s):  
Invasive Species ◽  
Evolutionary Ecology ◽  
Clonal Diversity ◽  
Invasion Biology ◽  
Metastatic Potential ◽  
Cancer Type ◽  
Primary Tumors ◽  
Invasion Genetics ◽  
Genome Level ◽  
Cancer Studies

The concept of invasion is useful across a broad range of contexts, spanning from the fine scale landscape of cancer tumors up to the broader landscape of ecosystems. Invasion biology provides extraordinary opportunities for studying the mechanistic basis of contemporary evolution at the molecular level. Although the field of invasion genetics was established in ecology and evolution more than 50 years ago, there is still a limited understanding of how genomic level processes translate into invasive phenotypes across different taxa in response to complex environmental conditions. This is largely because the study of most invasive species is limited by information about complex genome level processes. We lack good reference genomes for most species. Rigorous studies to examine genomic processes are generally too costly. On the contrary, cancer studies are fortified with extensive resources for studying genome level dynamics and the interactions among genetic and non-genetic mechanisms. Extensive analysis of primary tumors and metastatic samples have revealed the importance of several genomic mechanisms including higher mutation rates, specific types of mutations, aneuploidy or whole genome doubling and non-genetic effects. Metastatic sites can be directly compared to primary tumor cell counterparts. At the same time, clonal dynamics shape the genomics and evolution of metastatic cancers. Clonal diversity varies by cancer type, and the tumors’ donor and recipient tissues. Still, the cancer research community has been unable to identify any common events that provide a universal predictor of “metastatic potential” which parallels findings in evolutionary ecology. Instead, invasion in cancer studies depends strongly on context, including order of events and clonal composition. The detailed studies of the behavior of a variety of human cancers promises to inform our understanding of genome level dynamics in the diversity of invasive species and provide novel insights for management.

scholarly journals Targeting progesterone signaling prevents metastatic ovarian cancer

2020 ◽  
Vol 117 (50) ◽  
pp. 31993-32004
Author(s):  
Olga Kim ◽  
Eun Young Park ◽  
Sun Young Kwon ◽  
Sojin Shin ◽  
Robert E. Emerson ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Deleterious Mutation ◽  
Peritoneal Metastases ◽  
Cancer Development ◽  
Serous Carcinoma ◽  
Cancer Type ◽  
High Grade ◽  
Primary Tumors ◽  
High Risk Populations ◽  
Genetic Deletion

Effective cancer prevention requires the discovery and intervention of a factor critical to cancer development. Here we show that ovarian progesterone is a crucial endogenous factor inducing the development of primary tumors progressing to metastatic ovarian cancer in a mouse model of high-grade serous carcinoma (HGSC), the most common and deadliest ovarian cancer type. Blocking progesterone signaling by the pharmacologic inhibitor mifepristone or by genetic deletion of the progesterone receptor (PR) effectively suppressed HGSC development and its peritoneal metastases. Strikingly, mifepristone treatment profoundly improved mouse survival (∼18 human years). Hence, targeting progesterone/PR signaling could offer an effective chemopreventive strategy, particularly in high-risk populations of women carrying a deleterious mutation in the BRCA gene.

scholarly journals Metastatic Esophageal Carcinoma Cells Exhibit Reduced Adhesion Strength and Enhanced Thermogenesis

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1213
Author(s):  
Zihe Huo ◽  
Mariana Sá Santos ◽  
Astrid Drenckhan ◽  
Stefan Holland-Cunz ◽  
Jakob R. Izbicki ◽  
...  
Keyword(s):  
Esophageal Carcinoma ◽  
Tumor Cells ◽  
Cell Lines ◽  
Adhesion Strength ◽  
Primary Tumor ◽  
Carcinoma Cell ◽  
Metastatic Potential ◽  
Primary Tumors ◽  
Metastatic Cell ◽  
Carcinoma Cell Lines

Despite continuous improvements in multimodal therapeutic strategies, esophageal carcinoma maintains a high mortality rate. Metastases are a major life-limiting component; however, very little is known about why some tumors have high metastatic potential and others not. In this study, we investigated thermogenic activity and adhesion strength of primary tumor cells and corresponding metastatic cell lines derived from two patients with metastatic adenocarcinoma of the esophagus. We hypothesized that the increased metastatic potential of the metastatic cell lines correlates with higher thermogenic activity and decreased adhesion strength. Our data show that patient-derived metastatic esophageal tumor cells have a higher thermogenic profile as well as a decreased adhesion strength compared to their corresponding primary tumor cells. Using two paired esophageal carcinoma cell lines of primary tumor and lymph nodes makes the data unique. Both higher specific thermogenesis profile and decreased adhesion strength are associated with a higher metastatic potential. They are in congruence with the clinical patient presentation. Understanding these functional, biophysical properties of patient derived esophageal carcinoma cell lines will enable us to gain further insight into the mechanisms of metastatic potential of primary tumors and metastases. Microcalorimetric evaluation will furthermore allow for rapid assessment of new treatment options for primary tumor and metastases aimed at decreasing the metastatic potential.

scholarly journals Pivotal Role of AKT2 during Dynamic Phenotypic Change of Breast Cancer Stem Cells

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1058 ◽  
Author(s):  
Gener ◽  
Rafael ◽  
Seras-Franzoso ◽  
Perez ◽  
Pindado ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Cancer Stem Cells ◽  
Epithelial To Mesenchymal Transition ◽  
Distant Metastases ◽  
Metastatic Potential ◽  
Phenotypic Change ◽  
Primary Tumors ◽  
Mesenchymal Transition

Therapeutic resistance seen in aggressive forms of breast cancer remains challenging for current treatments. More than half of the patients suffer from a disease relapse, most of them with distant metastases. Cancer maintenance, resistance to therapy, and metastatic disease seem to be sustained by the presence of cancer stem cells (CSC) within a tumor. The difficulty in targeting this subpopulation derives from their dynamic interconversion process, where CSC can differentiate to non-CSC, which in turn de-differentiate into cells with CSC properties. Using fluorescent CSC models driven by the expression of ALDH1A 1(aldehyde dehydrogenase 1A1), we confirmed this dynamic phenotypic change in MDA-MB-231 breast cancer cells and to identify Serine/Threonine Kinase 2 (AKT2) as an important player in the process. To confirm the central role of AKT2, we silenced AKT2 expression via small interfering RNA and using a chemical inhibitor (CCT128930), in both CSC and non-CSC from different cancer cell lines. Our results revealed that AKT2 inhibition effectively prevents non-CSC reversion through mesenchymal to epithelial transition, reducing invasion and colony formation ability of both, non-CSC and CSC. Further, AKT2 inhibition reduced CSC survival in low attachment conditions. Interestingly, in orthotopic tumor mouse models, high expression levels of AKT2 were detected in circulating tumor cells (CTC). These findings suggest AKT2 as a promising target for future anti-cancer therapies at three important levels: (i) Epithelial-to-mesenchymal transition (EMT) reversion and maintenance of CSC subpopulation in primary tumors, (ii) reduction of CTC and the likelihood of metastatic spread, and (iii) prevention of tumor recurrence through inhibition of CSC tumorigenic and metastatic potential.

scholarly journals Invasion biology: critique of a pseudoscience

2004 ◽  
Vol 10 (1) ◽  
pp. 70
Author(s):  
Michael Calver
Keyword(s):  
Invasive Species ◽  
Invasion Biology ◽  
Rigorous Evaluation ◽  
Empirical Tests

Science is both highly competitive and highly cooperative, so a rigorous evaluation of an idea comes not from one's close colleagues, but from one's opponents (Hull 1988). While robust disagreement may not lead to consensus, at its best it should lead to clarification of areas of agreement and areas of dispute, as well as dialogue on the empirical tests necessary to solve the disagreements. In this context, David Theodoropoulos' new book on invasion biology attempts a rigorous, sceptical critique of the belief that invasive species are a significant threat to biodiversity.

scholarly journals Matrix metalloproteinase 14 (MMP14) is differentially expressed in breast cancer metastases.

2020 ◽  
Author(s):  
Shahan Mamoor
Keyword(s):  
Breast Cancer ◽  
Matrix Metalloproteinase ◽  
Messenger Rna ◽  
Metastatic Breast ◽  
Metastatic Potential ◽  
Primary Breast Tumor ◽  
Genomic Locus ◽  
Primary Tumors ◽  
Breast Cancer Metastases ◽  
Public Datasets

Breast cancer is a leading cause of death for women (1, 2). We mined public datasets to understand the most significant transcriptional and epigenomic changes between primary tumors of the breast and the metastases that they generate (3-6). In metastases to both the brain (3) and the bones (4), the matrix metalloproteinase 14 (MMP14) was among the genes whose expression changes most significantly between the transcriptomes of metastatic tissue to that of primary breast tumor. In metastases to the lymph nodes, a site at the MMP14 genomic locus contained significantly less methyl marks than the same site in primary tumors. The MMP14 gene was hypomethylated during spread of the breast cancer to the lymph node, MMP14 among the genes whose expression changed most significantly across the entire brain and bone transcriptome, and MMP14 messenger RNA was expressed at significantly lower levels in metastases across both tissues. Interestingly, primary tumors with metastatic potential expressed higher levels of MMP14 than primary tumors without metastatic potential. MMP14 is a target of interest in metastatic breast cancer.

scholarly journals Abstract 3910: Analysis of metastatic potential by breast cancer type through a microfluidic blood-brain niche

2017 ◽  
Author(s):  
Christopher Ryan Oliver ◽  
Megan Altemus ◽  
Brendan Leung ◽  
Aki Morikawa ◽  
Michele Dziubinski ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Potential ◽  
Cancer Type ◽  
Blood Brain ◽  
Breast Cancer Type

scholarly journals Distinct organ-specific metastatic potential of individual breast cancer cells and primary tumors

2005 ◽  
Vol 115 (1) ◽  
pp. 44-55 ◽  
Author(s):  
Andy J. Minn ◽  
Yibin Kang ◽  
Inna Serganova ◽  
Gaorav P. Gupta ◽  
Dilip D. Giri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Potential ◽  
Primary Tumors ◽  
Organ Specific

Oncology precision medicine for hepatobiliary and pancreatic cancer: An institutional review.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e14626-e14626
Author(s):  
Geoffrey Bellini ◽  
Jennifer Jo Godden ◽  
James L. Weese ◽  
Aaron Chevinsky ◽  
Wesley Allan Papenfuss ◽  
...  
Keyword(s):  
Precision Medicine ◽  
Genetic Alterations ◽  
Molecular Testing ◽  
Cancer Type ◽  
Extrahepatic Cholangiocarcinoma ◽  
Term Outcome ◽  
Primary Tumors ◽  
Long Term Outcome ◽  
Molecular Alterations ◽  
Number Of Patients

e14626 Background: Hepatobiliary cancers - hepatocellular carcinoma (HCC), intra or extrahepatic cholangiocarcinoma (I/EC), and gallbladder carcinoma (GB) - and pancreatic adenocarcinoma (PC) remain a leading cause of death with little improvement in long-term outcome. Recent studies have suggested that these cancers harbor actionable mutations to varying degrees. The aim of our study was to examine the number of patients (Pts) with these primary tumors who underwent molecular testing in a large vertically integrated health system. Subsequently, we analyzed the percentage of that population who may be candidates for oncology precision medicine (OPM) directed therapy. Methods: We identified Pts with HCC, IC, EC, GB in an IRB reviewed OPM database of our system over a one year period. Pts who underwent molecular panel testing were selected out, and their molecular alterations were identified and stratified by cancer type. Results: 304 total Pts were identified. 61 (20%) underwent molecular testing broken down as follows: 17/132 (13%) I/EC and HCC, 3/11 (27%) GB, and 41/161 (25%) PC. Quantity not sufficient for testing was in 10/61 (16%), of which 5/10 (50%) were resubmitted and tested successfully. 6/61 (10%) were cancelled or deemed not appropriate. Test recommended potential actionability was 8/17 (47%) of I/EC and HCC, 2/3 (67%) of GB, and 25/41 (61%) of PC. Conclusions: OPM is a dynamic area of increasing testing and learning. We found 13-27% of hepatobiliary and pancreatic Pts had molecular testing, which suggests the potential to increase molecular screening for this difficult group of tumors. Total genetic alterations (TGA) and clinically relevant genomic alterations (CRGA) per patient are similar to Ross et al. ( http://ow.ly/k52a30nBMnU ) for GB. Final interpretation regarding pragmatic actionability (patient on drug) and clinical outcomes are still under investigation.[Table: see text]

Tumor heterogeneity and drug resistance.

1986 ◽  
Vol 4 (2) ◽  
pp. 244-257 ◽  
Author(s):  
D L Dexter ◽  
J T Leith
Keyword(s):  
Drug Resistance ◽  
Tumor Heterogeneity ◽  
Metastatic Potential ◽  
Primary Tumors ◽  
Multiple Tumor ◽  
Underlying Basis ◽  
Human Solid Tumors ◽  
History Of ◽  
Relationship Of ◽  
The Impact

Drug resistance has long been identified as a major reason for therapy failure in cancer patients. Concurrently, work from many laboratories in the past 10 years has established tumor heterogeneity as a phenomenon of critical importance in the natural history of individual neoplasms. The two most sinister aspects of intraneoplastic diversity in human solid tumors are the genesis of clones with metastatic potential, and the existence of drug-resistant variants in primary cancers and their metastases. Thus, recent investigations on drug resistance and on tumor heterogeneity have converged to focus attention on the clonal organization of primary tumors and their metastases as the underlying basis for anticancer drug resistance. This review examines the degree of heterogeneity observed within tumors and the relationship of this diversity to resistance that might be anticipated for any given agent. A question critical to our discussion is "How many subpopulations are there?" The impact of multiple tumor clones on therapy is next discussed in relationship to normal tissue tolerance, the barrier clinicians face regardless of the specific agent used in treatment. Finally, laboratory and clinical approaches are presented for addressing a drug resistance problem that is seemingly overwhelming because of its complex biological roots.

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