Papillary Renal Cell Carcinomas Demonstrating Micropapillary Features: An Investigation Into the Diagnostic and Prognostic Implications.

AIMS: Papillary renal cell carcinoma (PRCC) with micropapillary carcinoma (MC) has been rarely described. We conducted a retrospective descriptive evaluation of the association of MC with PRCC and the possible prognostic implications. METHODS: A database search was made at the University of Southern California (USC) and Lenox Hill Hospital (LHH; New York City) in June 2016-June 2019 of PRCC cases with MC. Diagnosis of MC was made using routine histology, based on the presence of small clusters of cells without a vascular core. Features evaluated included: percent of MC, gross appearance, PRCC typing, nuclear grade, lymphovascular invasion, and lymph node metastasis. RESULTS: 848 RCC cases (690 from USC and 157 from LHH); 70 cases PRCC (54 from USC, 16 from LHH) of these cases, 13 had an MC, 12 were from radical nephrectomy, and 12 cases were male. Mean age was 68.3 years; seven were located in the right kidney. Average tumor size was 8.6 cm. MC ranged from 10% to 80% (average 37.5%), nine cases were PRCC type 2 and four type 1. Nuclear grade: three cases (grade 2), nine cases (grade 3), and one case (grade 4); 11 out of 13 tumors presented with extrarenal extension; nine cases that had lymph nodes submitted had metastatic carcinoma. CONCLUSIONS: The presence of a micropapillary component in PRCC was found to be 18.5%, and it was predominantly associated with high pathologic stage and lymph node metastases. The clinical course of these tumors seems similar to MC in other tissues/organ systems. We advocate reporting this pattern when identified.

In vitro effects of resistin on epithelial to mesenchymal transition (EMT) in MCF-7 and MDA-MB-231 breast cancer cells - qRT-PCR and Westen blot analyses data.

Resistin is an adipokine produced by the white adipocytes and adipose-derived macrophages, which mediates inflammation and insulin resistance Huang et al., 1997 and Renehan et al., 2008 Feb. Here, we provide data on the effect of resistin on epithelial to mesenchymal transition (EMT) in breast cancer cells in vitro. As model systems, we used human MCF-7 (low-metastatic) and MDA-MB-231 (high-metastatic) breast cancer cell lines. To optimize experimental conditions, we treated the cells with various concentrations of resistin (12.5, 25 and 50 ng/ml) for different time intervals (6 and 24 hours), and measured SOCS3 mRNA expression by using qRT-PCR analysis. Further, we used qRT-PCR and Western blot analyses to measure the expression of various epithelial (E-cadherin, claudin-1) and mesenchymal (SNAIL, SLUG, ZEB1, TWIST1, fibronectin, and vimentin) markers after resistin treatment. This data article is part of a study Avtanski et al., 2019 May, where detailed interpretation and discussion can be found.

Resistin induces breast cancer cells epithelial to mesenchymal transition (EMT) and stemness through both adenylyl cyclase-associated protein 1 (CAP1)-dependent and CAP1-independent mechanisms.

Breast cancer incidence and metastasis in postmenopausal women are known to associate with obesity, but the molecular mechanisms behind this association are largely unknown. We investigated the effect of adipokine resistin on epithelial to mesenchymal transition (EMT) and stemness in breast cancer cells in vitro. Previous reports demonstrated that the inflammatory actions of resistin are mediated by the adenylyl cyclase-associated protein 1 (CAP1), which serves as its receptor. As a model for our study, we used MCF-7 and MDA-MB-231 breast cancer and MCF-10A breast epithelial cells. We showed that in MCF-7 cells resistin increases the migration of MCF-7 and MDA-MB-231 cells and induces the formation of cellular protrusions through reorganization of F-actin filaments. Resistin upregulated the expression of mesenchymal markers involved in EMT (SNAIL, SLUG, ZEB1, TWIST1, fibronectin, and vimentin), and downregulated those of epithelial markers (E-cadherin and claudin-1). Resistin also potentiated the nuclear translocation of SNAIL protein, indicating initiation of EMT reprogramming. We further induced EMT in non-carcinogenic breast epithelial MCF-10A cells demonstrating that the effects of resistin on EMT were not breast cancer cell specific. In order to assess whether resistin-induced EMT depends on CAP1, we used siRNA approach to silence CAP1 gene in MCF-7 cells. Results demonstrated that when CAP1 was silenced, the induction of SNAIL, ZEB1 and vimentin expression by resistin as well as SNAIL and ZEB1 nuclear translocation, were abolished. Additionally, CAP1 silencing resulted in a suppression of MCF-7 cells migration. We performed quantitative PCR array profiling the expression of 84 genes related to cancer stem cells (CSC), pluripotency and metastasis and selected a set of genes (ALDH1A1, ITGA4, LIN28B, SMO, KLF17, PTPRC, PROM1, SIRT1, and PECAM1) that were modulated by resistin. Further experiments demonstrated that the effect of resistin on the expression of some of these genes (PROM1, PTPRC, KLF17, SIRT1, and PECAM1) was also dependent on CAP1. Our results demonstrate that resistin promotes the metastatic potential of breast cancer cells by inducing EMT and stemness and some of these effects are mediated by CAP1.