Biology subjects

Payne, S. L.

Publications and source records attributed to Payne, S. L..

4 recordsLinked to original sources

bioRxiv2023

Cell morphology best predicts tumorigenicity and metastasis in vivo across multiple TNBC cell lines of different metastatic potential

BackgroundMetastasis is the leading cause of death in breast cancer patients. For metastasis to occur, tumor cells must invade locally, intravasate, and colonize distant tissues and organs, all steps that require tumor cell migration. The majority of studies on invasion and metastasis rely on human breast cancer cell lines. While it is known that these cells have different properties and abilities for growth and metastasis, the in vitro morphological, proliferative, migratory, and invasive behavior of these cell lines and their correlation to in vivo behavior is poorly understood. Thus, we sought to classify each cell line as poorly or highly metastatic by characterizing tumor growth and metastasis in a murine model of six commonly used human triple-negative breast cancer xenografts, as well as determine which in vitro assays commonly used to study cell motility best predict in vivo metastasis. MethodsWe evaluated the liver and lung metastasis of human TNBC cell lines MDA-MB-231, MDA-MB-468, BT549, Hs578T, BT20, and SUM159 in immunocompromised mice. We characterized each cell lines cell morphology, proliferation, and motility in 2D and 3D to determine the variation in these parameters between cell lines. ResultsWe identified MDA-MB-231, MDA-MB-468, and BT549 cells as highly tumorigenic and metastatic, Hs578T as poorly tumorigenic and metastatic, BT20 as intermediate tumorigenic with poor metastasis to the lungs but highly metastatic to the livers, and SUM159 as intermediate tumorigenic but poorly metastatic to the lungs and livers. We showed that metrics that characterize cell morphology are the most predictive of tumor growth and metastatic potential to the lungs and liver. Further, we found that no single in vitro motility assay in 2D or 3D significantly correlated with metastasis in vivo. ConclusionsOur results provide an important resource for the TNBC research community, identifying the metastatic potential of 6 commonly used cell lines. Our findings also support the use of cell morphological analysis to investigate the metastatic potential and emphasize the need for multiple in vitro motility metrics using multiple cell lines to represent the heterogeneity of metastasis in vivo.

cancer biology↗

bioRxiv2021

Sensory nerves enhance triple-negative breast cancer migration and metastasis via the axon guidance molecule PlexinB3

In breast cancer, nerve presence has been correlated with more invasive disease and worse prognosis, yet the mechanisms by which different types of peripheral nerves drive tumor progression remain poorly understood. In this study, we identified sensory nerves as more abundant in human triple-negative breast cancer (TNBC) tumors. Coinjection of sensory neurons isolated from the dorsal root ganglia (DRG) of adult female mice with human TNBC cells in immunocompromised mice increased the number of lung metastases. Direct in vitro co-culture of human TNBC cells with the dorsal root ganglia (DRG) of adult female mice revealed that TNBC cells adhere to sensory neuron fibers leading to an increase in migration speed. Species-specific RNA sequencing revealed that co-culture of TNBC cells with sensory nerves upregulates the expression of genes associated with cell migration and adhesion in cancer cells. We demonstrate that the axon guidance molecule Plexin B3 mediates cancer cell adhesion to and migration on sensory nerves. Together, our results identify a novel mechanism by which nerves contribute to breast cancer migration and metastasis by inducing a shift in TNBC cell gene expression and support the rationale for disrupting neuron-cancer cell interactions to target metastasis. SignificanceThe presence of nerves in breast tumors has been associated with poor outcome. Understanding the mechanisms by which nerves contribute to tumor progression could help identify novel strategies to target metastatic disease.

cancer biology↗

bioRxiv2021

Potassium channel-driven bioelectric signaling regulates metastasis in triple-negative breast cancer

There is a critical need to better understand the mechanisms that drive local cell invasion and metastasis to develop new therapeutics targeting metastatic disease. Bioelectricity is an important mediator of cellular processes and changes in the resting membrane potential (RMP) are associated with increased cancer cell invasion. However, the mechanism is not well understood. Our data demonstrate that altering the RMP of triple-negative breast cancer (TNBC) cells by manipulating potassium channel expression increases in vitro invasion, in vivo tumor growth, and metastasis, and is accompanied by changes in gene expression associated with cell adhesion. We describe a novel mechanism for RMP-mediated cell migration involving cadherin-11 and the MAPK pathway. Importantly, we identify a new strategy to target metastatic TNBC in vivo by repurposing FDA-approved potassium channel blockers. Our results provide an understanding of the mechanisms by which bioelectricity regulates cancer cell invasion and metastasis that could lead to a new class of therapeutics for patients with metastatic disease.

cancer biology↗

bioRxiv2019

Defined extracellular ionic solutions to study and manipulate the cellular resting membrane potential

All cells possess an electric potential across their plasma membranes. While familiar in the context of excitable cells such as neurons, healthy non-excitable cells are also able to generate and receive bioelectric signals. The cellular resting membrane potential (RMP) regulates many factors in cell homeostasis, such as cell proliferation, differentiation and apoptosis. It is therefore critical to develop simple strategies to measure, manipulate and characterize this feature. Current studies to evaluate RMP rely on the patch clamp approach, which is technically challenging, low-throughput and not widely available to the scientific community. Here, we present a relatively simple methodology to functionally study the role of RMP in non-excitable cells by modulating it pharmacologically, and using a voltage-sensitive dye to characterize the contribution of individual ions to the RMP. Specifically, we define protocols for using extracellular solutions in which permeable ions (Na+, Cl- and K+) are substituted with non-permeable ions (N-Methyl-D-glucamine (NMDG), gluconate, choline, SO42-) to study and manipulate RMP in vitro. The resulting RMP modifications were assessed with both patch clamp and a voltage sensitive dye. Using an epithelial and cancer cell line, we demonstrate that the proposed ionic solutions can determine the relative contribution of ionic species in setting the RMP and be used to actively and selectively modify the RMP. The proposed method is simple and reproducible and will make the study of bioelectricity more readily available to the cell biology community by enabling functional modulation of RMP in most cellular assays.\n\nAuthor Disclosure StatementsNo competing financial interests exist.

cell biology↗