KISS1R Signaling Promotes Breast Cancer Metastasis

Kisspeptins, peptide products of KISS1, are endogenous ligands for KISS1R, a G protein-coupled receptor. In numerous cancers, KISS1 acts as a metastasis suppressor. However, studies have revealed that patients with elevated KISS1 and KISS1R breast tumor expression have increased tumor grade, increased lymph node metastases and poor survival. We hypothesize that depletion of KISS1R inhibits breast cancer cell metastasis. In order to assess the role of KISS1R in breast cancer metastasis, we used a pre-clinical orthotopic xenograft mouse model using MDA-MB-231 breast cancer cells for breast tumor establishment. We discovered that depletion of KISS1R decreased primary tumor growth and reduced lung metastatic burden, suggesting that KISS1R plays a role in promoting breast cancer metastasis. Furthermore, we observed that kisspeptin-10 stimulation increased breast cancer cell invadopodia formation via a β-arrestin2 dependent mechanism. Overall, our results suggest that KISS1R may be a novel therapeutic target in the prevention of breast cancer metastasis

G protein-coupled kisspeptin receptor induces metabolic reprograming and tumorigenesis in estrogen receptor-negative breast cancer

Triple-negative breast cancer (TNBC) is a highly metastatic and deadly disease. TNBC tumors lack estrogen receptor (ERα), progesterone receptor (PR), and HER2 (ErbB2) and exhibit increased glutamine metabolism, a requirement for tumor growth. The G protein-coupled kisspeptin receptor (KISS1R) is highly expressed in patient TNBC tumors and promotes malignant transformation of breast epithelial cells. This study found that TNBC patients displayed elevated plasma kisspeptin levels compared with healthy subjects. It also provides the first evidence that in addition to promoting tumor growth and metastasis in vivo, KISS1R-induced glutamine dependence of tumors. In addition, tracer-based metabolomics analyses revealed that KISS1R promoted glutaminolysis and nucleotide biosynthesis by increasing c-Myc and glutaminase levels, key regulators of glutamine metabolism. Overall, this study establishes KISS1R as a novel regulator of TNBC metabolism and metastasis, suggesting that targeting KISS1R could have therapeutic potential in the treatment of TNBC

Correction to: Three-Dimensional Quantification of Spheroid Degradation-Dependent Invasion and Invadopodia Formation

It has come to the authors’ attention that the representative image of the unstimulated UMSCC1 spheroid at Day 1 in Fig. 1a was selected from the wrong data set

Three-Dimensional Quantification of Spheroid Degradation-Dependent Invasion and Invadopodia Formation

Abstract Invadopodia are actin-rich, proteolytic structures that enable cancer cell to invade into the surrounding tissues. Several in vitro invasion assays have been used in the literature ranging from directional quantitative assays to complex three-dimensional (3D) analyses. One of the main limitations of these assays is the lack of quantifiable degradation-dependent invasion in a three-dimensional (3D) environment that mimics the tumor microenvironment. In this article, we describe a new invasion and degradation assay based on the currently available tumor spheroid model that allows long-term high-resolution imaging of the tumor, precise quantification, and visualization of matrix degradation and multichannel immunocytochemistry. By incorporating a degradation marker (DQ-Green BSA) into a basement-membrane matrix, we demonstrate the ability to quantitate cancer cell-induced matrix degradation in 3D. Also, we describe a technique to generate histological sections of the tumor spheroid allowing the detection of invadopodia formation in the 3D tumor spheroid. This new technique provides a clear advantage for studying cancer in vitro and will help address critical questions regarding the dynamics of cancer cell invasion

A Novel, Combined Student and Preceptor Professional Development Session for Optimizing Feedback: Protocol for a Multimethod, Multisite, and Multiyear Intervention

BackgroundProviding feedback to medical learners is a critical educational activity. Despite the recognition of its importance, most research has focused on training preceptors to give feedback, which neglects the role of learners in receiving feedback. Delivering a combined professional development session for both preceptors and students may facilitate more effective feedback communication and improve both the quality and quantity of feedback. ObjectiveThe objective of our research project is to examine the impact of a relational feedback intervention on both preceptors and students during a longitudinal integrated clerkship. MethodsStudents and preceptors will attend a 2.5-hour combined professional development session, wherein they will be provided with educational tools for giving and receiving feedback within a coaching relationship and practice feedback giving and receiving skills together. Before the combined professional development session, students will be asked to participate in a 1-hour preparation session that will provide an orientation on their role in receiving feedback and their participation in the combined professional development session. Students and preceptors will be asked to complete a precombined professional development session survey and an immediate postcombined professional development session survey. Preceptors will be asked to complete a follow-up assessment survey, and students will be asked to participate in a follow-up, student-only focus group. Anonymized clinical faculty teaching evaluations and longitudinal integrated clerkship program evaluations will also be used to assess the impact of the intervention. ResultsAs of March 1, 2022, a total of 66 preceptors and 29 students have completed the baseline and follow-up measures. Data collection is expected to conclude in December 2023. ConclusionsOur study is designed to contribute to the literature on the feedback process between preceptors and students within a clinical setting. Including both the preceptors and the students in the same session will improve on the work that has already been conducted in this area, as the students and preceptors can further develop their relationships and coconstruct feedback conversations. We will use social learning theory to interpret the results of our study, which will help us explain the results and potentially make the work generalizable to other fields. International Registered Report Identifier (IRRID)DERR1-10.2196/3282

The effects of lateral meniscal allograft transplantation techniques on tibio-femoral contact pressures.

Accepted versio