ABSTRACT
Current therapy for pancreatic cancer is multimodal, involving surgery and chemotherapy. However, development of pancreatic cancer therapies requires a thorough evaluation of drug efficacy in vitro before animal testing and subsequent clinical trials. Compared to two-dimensional culture of cell monolayer, three-dimensional (3-D) models more closely mimic native tissues, since the tumor microenvironment established in 3-D models often plays a significant role in cancer progression and cellular responses to the drugs. Accumulating evidence has highlighted the benefits of 3-D in vitro models of various cancers. In the present study, we have developed a spheroid-based, 3-D culture of pancreatic cancer cell lines MIAPaCa-2 and PANC-1 for pancreatic drug testing, using the acid phosphatase assay. Drug efficacy testing showed that spheroids had much higher drug resistance than monolayers. This model, which is characteristically reproducible and easy and offers rapid handling, is the preferred choice for filling the gap between monolayer cell cultures and in vivo models in the process of drug development and testing for pancreatic cancer.
Subject(s)
Humans , Acid Phosphatase/metabolism , Drug Screening Assays, Antitumor/methods , Pancreatic Neoplasms/drug therapy , Spheroids, Cellular/drug effects , Antimetabolites, Antineoplastic/administration & dosage , Cell Survival , Cell Culture Techniques/methods , Cell Line, Tumor/drug effects , Cell Line, Tumor/enzymology , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Fluorouracil/administration & dosage , Pancreatic Neoplasms/enzymology , Spheroids, Cellular/enzymologyABSTRACT
Pancreatic cancer is a notorious disease with a poor prognosis and low survival rates, which is due to limited advances in understanding of the molecular mechanism and inadequate development of effective treatment options over the decades. In previous studies, we demonstrated that a novel soluble protein named pancreatic adenocarcinoma up-regulated factor (PAUF) acts on tumor and immune cells and plays an important role in metastasis and progression of pancreatic cancer. Here we show that PAUF promotes adhesiveness of pancreatic cancer cells to various extracellular matrix (ECM). Our results further support a positive correlation of activation and expression of focal adhesion kinase (FAK), a key player in tumor cell metastasis and survival, with PAUF expression. PAUF-mediated adhesiveness was significantly attenuated upon blockade of the FAK pathway. Moreover, PAUF appeared to enhance resistance of pancreatic cancer cells to anoikis via modulation of FAK. Our results suggest that PAUF-mediated FAK activation plays an important role in pancreatic cancer progression.
Subject(s)
Humans , Anoikis/genetics , Cell Line, Tumor , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Focal Adhesions/genetics , Lectins/genetics , Pancreatic Neoplasms/enzymology , Proto-Oncogene Proteins pp60(c-src)/metabolism , Signal Transduction/geneticsABSTRACT
Os achados clínicos, laboratoriais e radiológicos de 25 doentes com câncer de cabeça do pâncreas foram comparados com os mesmos dados obsrvados em 25 doentes com pancreatite crönica alcoólica e colestase. Antecedentes de alcoolismo, presença de prurido e vesícula palpável foram os dados clínicos importantes no diagníóstico difencial. Os níveis de bilirrubina plasmática foram mais elevados no câncer do pâncreas (20 + ou - 14,3 vs. 2,5 + ou - 2,4), näo havendo diferença entre os doisgrupos na evoluçäo dos níveis após internaçäo. O ultra-som pré-operatório, assim como os achados colangiográficos pré e intra-operatórios, permitiu a diferenciaçäo das duas patologias, na maioria dos casos. O sistema de avaliaçäo por pontos, baseado nas diferenças clínicas, laboratoriais e radiológicas, apresentou uma sensibilidade de 100% para pancreatite crônica e 96% para o câncer do pânreas