Metastasis to the bone marrow is observed in a number of fatal cancers. Tumor cells preferentially migrate to the bone cavity as a function of composition of the bone marrow. We have developed a tissue engineered analogue of the bone marrow and plan to use this construct to identify the key stromal cellular components of a bone marrow metastatic niche. We propose to: 1) Develop a microfluidic platform to capture migratory tumor cells in vitro, 2) Create tumor-stroma microenvironments on-chip, and 3) In vivo comparison and treatment study of BMSC scaffolds on tumor growth. This project will provide essential training to candidate in microfluidics, imaging, and cancer biology during the K99 training period and propel him to be a successful independent investigator in the field of biomaterials and oncology as an R00 investigator at a research university.

Public Health Relevance

Tumor cell metastasis is an insidious phenomenon that causes 90% of cancer-associated death and the bone marrow has been recognized as a prime and early metastatic site of numerous tumors. The objective of proposed research is to elucidate essential stromal components of bone marrow niche that are the linchpin of a tumor metastasis using engineered bone marrow tissue models. The results of this study are expected to directly improve public health by providing alternative therapeutic strategies for preventing bone marrow metastasis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Transition Award (R00)
Project #
4R00CA163671-03
Application #
8903811
Study Section
Special Emphasis Panel (NSS)
Program Officer
Kuhn, Nastaran Z
Project Start
2014-09-10
Project End
2017-08-31
Budget Start
2014-09-10
Budget End
2015-08-31
Support Year
3
Fiscal Year
2014
Total Cost
$241,527
Indirect Cost
$83,109
Name
University of Massachusetts Amherst
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
153926712
City
Amherst
State
MA
Country
United States
Zip Code
01003
Lee, Jungwoo; Heckl, Dirk; Parekkadan, Biju (2016) Multiple genetically engineered humanized microenvironments in a single mouse. Biomater Res 20:19
Lee, Jungwoo; Kohl, Nathaniel; Shanbhang, Sachin et al. (2015) Scaffold-integrated microchips for end-to-end in vitro tumor cell attachment and xenograft formation. Technology (Singap World Sci) 3:179-188
Bersani, Francesca; Lee, Jungwoo; Yu, Min et al. (2014) Bioengineered implantable scaffolds as a tool to study stromal-derived factors in metastatic cancer models. Cancer Res 74:7229-38
Shen, Keyue; Lee, Jungwoo; Yarmush, Martin L et al. (2014) Microcavity substrates casted from self-assembled microsphere monolayers for spheroid cell culture. Biomed Microdevices 16:609-15