Abstract
Multiple changes within the tumor microenvironment have been correlated with an increase in metastasis, yet the mechanisms are not fully understood. Tumor cells can be stimulated by the release of chemoattractant factors such as epidermal growth factor (EGF) from nearby stromal cells, resulting in increased intravasation and metastasis. Additionally, altered extracellular matrix density can result in changes in gene expression patterns governing increased cellular proliferation and motility. The Nano Intravital Device (NANIVID) has been used to produce gradients of select soluble factors in the tumor microenvironment and to study the role of these changes on cell migration. In previous studies, the NANIVID utilized a synthetic hydrogel to produce an EGF gradient to attract metastatic breast cancer cells. In this work, a matrigel insert will be introduced into the outlet to provide a substrate for cells to migrate on when entering the device. The concentration of the chemoattractant and matrigel comprising the insert will be optimized to produce a suitable gradient for inducing chemotaxis in metastatic breast cancer cells in vitro. Additionally, silk and alginate matrices will be explored as improved soluble factor release mediums. Delivery of larger molecules such as collagen cross-linkers requires an alternative hydrogel material. Future NANIVID experiments will utilize these materials to gauge the cellular motility response when a stiffer matrix is encountered.
| Original language | English (US) |
|---|---|
| Title of host publication | Proceedings of SPIE - The International Society for Optical Engineering |
| Volume | 8615 |
| DOIs | |
| State | Published - 2013 |
| Event | Microfluidics, BioMEMS, and Medical Microsystems XI - San Francisco, CA, United States Duration: Feb 3 2013 → Feb 5 2013 |
Other
| Other | Microfluidics, BioMEMS, and Medical Microsystems XI |
|---|---|
| Country | United States |
| City | San Francisco, CA |
| Period | 2/3/13 → 2/5/13 |
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Keywords
- alginate
- hydrogel
- metastasis
- silk
- tumor microenvironment
ASJC Scopus subject areas
- Applied Mathematics
- Computer Science Applications
- Electrical and Electronic Engineering
- Electronic, Optical and Magnetic Materials
- Condensed Matter Physics
Cite this
Optimized release matrices for use in a BioMEMS device to study metastasis. / Clark, Ashley; Williams, James; Padgen, Michael; Keely, Patricia; Condeelis, John S.; Castracane, James.
Proceedings of SPIE - The International Society for Optical Engineering. Vol. 8615 2013. 86150C.Research output: Chapter in Book/Report/Conference proceeding › Conference contribution
}
TY - GEN
T1 - Optimized release matrices for use in a BioMEMS device to study metastasis
AU - Clark, Ashley
AU - Williams, James
AU - Padgen, Michael
AU - Keely, Patricia
AU - Condeelis, John S.
AU - Castracane, James
PY - 2013
Y1 - 2013
N2 - Multiple changes within the tumor microenvironment have been correlated with an increase in metastasis, yet the mechanisms are not fully understood. Tumor cells can be stimulated by the release of chemoattractant factors such as epidermal growth factor (EGF) from nearby stromal cells, resulting in increased intravasation and metastasis. Additionally, altered extracellular matrix density can result in changes in gene expression patterns governing increased cellular proliferation and motility. The Nano Intravital Device (NANIVID) has been used to produce gradients of select soluble factors in the tumor microenvironment and to study the role of these changes on cell migration. In previous studies, the NANIVID utilized a synthetic hydrogel to produce an EGF gradient to attract metastatic breast cancer cells. In this work, a matrigel insert will be introduced into the outlet to provide a substrate for cells to migrate on when entering the device. The concentration of the chemoattractant and matrigel comprising the insert will be optimized to produce a suitable gradient for inducing chemotaxis in metastatic breast cancer cells in vitro. Additionally, silk and alginate matrices will be explored as improved soluble factor release mediums. Delivery of larger molecules such as collagen cross-linkers requires an alternative hydrogel material. Future NANIVID experiments will utilize these materials to gauge the cellular motility response when a stiffer matrix is encountered.
AB - Multiple changes within the tumor microenvironment have been correlated with an increase in metastasis, yet the mechanisms are not fully understood. Tumor cells can be stimulated by the release of chemoattractant factors such as epidermal growth factor (EGF) from nearby stromal cells, resulting in increased intravasation and metastasis. Additionally, altered extracellular matrix density can result in changes in gene expression patterns governing increased cellular proliferation and motility. The Nano Intravital Device (NANIVID) has been used to produce gradients of select soluble factors in the tumor microenvironment and to study the role of these changes on cell migration. In previous studies, the NANIVID utilized a synthetic hydrogel to produce an EGF gradient to attract metastatic breast cancer cells. In this work, a matrigel insert will be introduced into the outlet to provide a substrate for cells to migrate on when entering the device. The concentration of the chemoattractant and matrigel comprising the insert will be optimized to produce a suitable gradient for inducing chemotaxis in metastatic breast cancer cells in vitro. Additionally, silk and alginate matrices will be explored as improved soluble factor release mediums. Delivery of larger molecules such as collagen cross-linkers requires an alternative hydrogel material. Future NANIVID experiments will utilize these materials to gauge the cellular motility response when a stiffer matrix is encountered.
KW - alginate
KW - hydrogel
KW - metastasis
KW - silk
KW - tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=84878143185&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878143185&partnerID=8YFLogxK
U2 - 10.1117/12.2005048
DO - 10.1117/12.2005048
M3 - Conference contribution
AN - SCOPUS:84878143185
SN - 9780819493842
VL - 8615
BT - Proceedings of SPIE - The International Society for Optical Engineering
ER -