The Tumor MicroEnvironment for Metastasis (TMEM) is a critical determinant which will presage the evolution of primary tumors and the resulting metastatic dynamics. Primary tumor cells up and down regulate certain genes which increase motility and cause a disregard for positional information. We report on the development of a new tool for the documentation of cancer cell migration (initial targets: the rat mammary adenocarcinoma cell lines MTLn3 with an over expression of Mena+++). This tool, the NANo IntraVital Device (NANIVID), is a multi-functional nanosystem composed of a chemoattractant source (hydrogel-EGF), capsule (cell trap), counter (transparent, interdigitated electrode arrays for sensing cell arrival), and remote reporter (readout electronics). The device will be retrieved from the tumor site and the cells will be expelled for subsequent assay. The NANIVID will be used in conjunction with the current catheter-based approach in which a needle is loaded with a chemoattractant source and injected into the tumor. A major drawback in the catheter approach is the short cell collection time and lack of real time registering and reporting of cell arrival. This paper will present the current status of the NANIVID prototypes developed in which a transparent implantable device is loaded with chemoattractant source and placed near candidate mammary gland tumors in an established rat model for multiple days or weeks. This series of experiments will allow the comparison of methods and to benchmark the NANIVID for use in research. Initial results of these experiments and NANIVID design modifications will be presented.
[1]
J. Segall,et al.
EGF stimulates an increase in actin nucleation and filament number at the leading edge of the lamellipod in mammary adenocarcinoma cells.
,
1998,
Journal of cell science.
[2]
J. Segall,et al.
The collection of the motile population of cells from a living tumor.
,
2000,
Cancer research.
[3]
James Castracane,et al.
The NANIVID: a new device for cancer cell migration studies
,
2008,
SPIE BiOS.
[4]
Erik Sahai,et al.
Macrophages promote the invasion of breast carcinoma cells via a colony-stimulating factor-1/epidermal growth factor paracrine loop.
,
2005,
Cancer research.
[5]
John Condeelis,et al.
Macrophages: Obligate Partners for Tumor Cell Migration, Invasion, and Metastasis
,
2006,
Cell.
[6]
John S. Condeelis,et al.
Identification and Testing of a Gene Expression Signature of Invasive Carcinoma Cells within Primary Mammary Tumors
,
2004,
Cancer Research.
[7]
D. Lauffenburger,et al.
A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis.
,
2008,
Developmental cell.