Pharmaceutica Analytica Acta

Study on interaction between cancer cells and mesenchymal stem cells via indirect or direct cellto- cell connection

2^nd World Congress on Bioavailability & Bioequivalence: Pharmaceutical R & D Summit-2011 and International Conference on Pharmaceutics & Novel Drug Delivery Systems

06-08 June 2011, Las Vegas, USA

Xiaohui Long

Scientific Tracks Abstracts: PAA

Abstract:

Mesenchymal stem cells (MSCs), identifi ed as a bone marrow-derived cell population, display self-renewal ability and can also diff erentiate into mesodermal lineages such as cartilage, adipose, connective tissue, and tendon. Recently, increasing evidence shows that MSCs could localize to the site of tumorigenesis and has important eff ects on cancer cells by providing cancer cells with essential microenvironment, but the relationship between stem cells and tumor cells and the mechanisms underlined are not clear. In the present study, we have examined the interaction between human cancer cells (HepG2 and Hela) and human MSCs (hMSCs) by the addition of conditioned medium obtained from coculture or by transwell culture (using a fi lter as an insert). For establishing direct cell-to-cell cocultivation, we have developed a nanoparticle-based diff erential labeling approach using internalizing quantum dots (i-QDs), which is a noninvasive and nondisruptive way to monitor and distinguish the co-cultured cells spatio-temporally. We demonstrate that tumor cells display decreased cell proliferation and increased cell death in dose-dependent manner as assessed by CCK-8 or DNA content assay. Th e growth-inhibitory eff ect is further confi rmed by performing cell cycle assay showing that cell cycle is arrested in the G 2 /M transition and the cell apoptotic rate exhibited higher level as compared to that without the presence of hMSCs. Furthermore, we show that labeled hMSCs traffi c from bone marrow migrate towards cancer cells for interaction under fl uorescence microscope at diff erent time points. Th is suggests that hMSCs, when co-cultured with cancer cells, interact with cancer cells and have important eff ect on the tumor cells growth. Additionally, we test whether the mitogen-activated protein kinase kinase (PI3K) and mitogen-activated protein kinase pathways, which play an important role in cell proliferation, diff erentiation, and tumorigenesis, are involved in hMSC- mediated regulation, and fi nd that protein kinase B (PKB), phosphorylated PKB (P-PKB), and extracellular signal-regulated kinases (ERK1/2) etc; key components of PI3K or MAPK pathway, signifi cantly decreased in the expressions as shown by using real-time quantitative reverse transcription polymerase chain reaction (QRT-PCR) and western blotting analysis. Th us it could be concluded from the results that hMSCs interact with cancer cells by providing them with microenvironment to regulate the tumor survival and growth, and the PI3K/MAPK signaling pathway activation is required for the induction of suppression of tumorigenesis by hMSCs. Th is would extend our understanding of the correlation between human MSCs and cancer cells, which might be important in developing novel interfering strategies for improved tumor therapy and drug discovery.

Biography :

Xiaohui Long has Ph.D in Biochemistry and Molecular Biology (2006). She is a staff senior researcher at the National Institute of Advanced Industrial Science and Technology (AIST), Japan. Her research group is currently working on the development of new labeling techniques for in vitro and in vivo tracking of cells and the application of new labelings? for screening the interaction between cancer cells and mesenchymal stem cells using fl uorescence microscope. She has 1 patent, published over 30 papers in Biology and Biochemistry journals, and serving as an member of National Chemistry Association .