Cell and Developmental Biology Commons^™

Epithelial-To-Mesenchymal Transition Leads To Disease-Stage Differences In Circulating Tumor Cell Detection And Metastasis In Pre-Clinical Models Of Prostate Cancer, Lori E. Lowes, David Goodale, Ying Xia, Carl Postenka, Matthew M. Piaseczny, Freeman Paczkowski, Alison L. Allan

Anatomy and Cell Biology Publications

Metastasis is the cause of most prostate cancer (PCa) deaths and has been associated with circulating tumor cells (CTCs). The presence of >= 5 CTCs/7.5mL of blood is a poor prognosis indicator in metastatic PCa when assessed by the CellSearch (R) system, the "gold standard" clinical platform. However, similar to 35% of metastatic PCa patients assessed by CellSearch (R) have undetectable CTCs. We hypothesize that this is due to epithelial-to-mesenchymal transition (EMT) and subsequent loss of necessary CTC detection markers, with important implications for PCa metastasis. Two pre-clinical assays were developed to assess human CTCs in xenograft models; one comparable …

Generation Of Organ-Conditioned Media And Applications For Studying Organ-Specific Influences On Breast Cancer Metastatic Behavior, Matthew M. Piaseczny, Graciella M. Pio, Jenny E. Chu, Ying Xia, Kim Nguyen, David Goodale, Alison Allan

Anatomy and Cell Biology Publications

Breast cancer preferentially metastasizes to the lymph node, bone, lung, brain and liver in breast cancer patients. Previous research efforts have focused on identifying factors inherent to breast cancer cells that are responsible for this observed metastatic pattern (termed organ tropism), however much less is known about factors present within specific organs that contribute to this process. This is in part because of a lack of in vitro model systems that accurately recapitulate the organ microenvironment. To address this, an ex vivo model system has been established that allows for the study of soluble factors present within different organ microenvironments. …

Recent Advances In The Molecular Characterization Of Circulating Tumor Cells, Lori E. Lowes, Alison L. Allan

Anatomy and Cell Biology Publications

Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch((R)) system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs …

Adaptation Of Semiautomated Circulating Tumor Cell (Ctc) Assays For Clinical And Preclinical Research Applications, Lori E. Lowes, Benjamin D. Hedley, Michael Keeney, Alison L. Allan

Anatomy and Cell Biology Publications

The majority of cancer-related deaths occur subsequent to the development of metastatic disease. This highly lethal disease stage is associated with the presence of circulating tumor cells (CTCs). These rare cells have been demonstrated to be of clinical significance in metastatic breast, prostate, and colorectal cancers. The current gold standard in clinical CTC detection and enumeration is the FDA-cleared CellSearch system (CSS). This manuscript outlines the standard protocol utilized by this platform as well as two additional adapted protocols that describe the detailed process of user-defined marker optimization for protein characterization of patient CTCs and a comparable protocol for CTC …

Centrosomal Kinase Nek2 Cooperates With Oncogenic Pathways To Promote Metastasis, T K. Das, Dibyendu Dana, Suneeta S. Paroly, S. K. Perumal, S. Singh, H. Jhun, J. Pendse, R. L. Cagan, T. T. Talele, Sanjai Kumar

Publications and Research

Centrosomal kinase Nek2 is overexpressed in different cancers, yet how it contributes toward tumorigenesis remains poorly understood. dNek2 overexpression in a Drosophila melanogaster model led to upregulation of Drosophila Wnt ortholog wingless (Wg), and alteration of cell migration markers—Rho1, Rac1 and E-cadherin (Ecad)—resulting in changes in cell shape and tissue morphogenesis. dNek2 overexpression cooperated with receptor tyrosine kinase and mitogen-activated protein kinase signaling to upregulate activated Akt, Diap1, Mmp1 and Wg protein to promote local invasion, distant seeding and metastasis. In tumor cell injection assays, dNek2 cooperated with Ras and Src signaling to promote aggressive colonization of tumors into different …

High Aldehyde Dehydrogenase And Expression Of Cancer Stem Cell Markers Selects For Breast Cancer Cells With Enhanced Malignant And Metastatic Ability, Alysha K. Croker, David Goodale, Jenny Chu, Carl Postenka, Benjamin D. Hedley, David A. Hess, Alison L. Allan

Anatomy and Cell Biology Publications

Cancer stem cells (CSCs) have recently been identified in leukaemia and solid tumours; however, the role of CSCs in metastasis remains poorly understood. This dearth of knowledge about CSCs and metastasis is due largely to technical challenges associated with the use of primary human cancer cells in pre-clinical models of metastasis. Therefore, the objective of this study was to develop suitable pre-clinical model systems for studying stem-like cells in breast cancer metastasis, and to test the hypothesis that stem-like cells play a key role in metastatic behaviour. We assessed four different human breast cancer cell lines (MDA-MB-435, MDA-MB-231, MDA-MB-468, MCF-7) …

Loss Of Ski Expression In Testicular Cancer Leads To An Enhanced Invasive Phenotype Through Both Bmp-Dependent And Bmp-Independent Pathways, Amy N. Nash

Theses, Dissertations and Capstones

The proto-oncogene SKI is a transcription factor and a co-repressor of the TGFβ superfamily, including TGF

β and BMP. However, additional data suggests that SKI may function as a tumor suppressor in some cell types. The TGFβ superfamily has been implicated in cancer progression and germ cell migration. Testicular cancer afflicts men during their peak reproductive years and is the most common cancer among men of this age group. Cisplatin-based chemotherapy is the standard treatment for testicular cancer. This treatment can lead to undesirable side effects, including infertility. We have shown that SKI expression is decreased in testicular germ cell …