Motility of cancer cells is a hallmark of metastasis - that is, a complex, multistage process, in which these cells acquire a tissue-invasive, directional motility phenotype, detach from primary tumors, migrate to distant sites, and colonize them to start new loci of disease. Although metastasis is the major cause of mortality in cancer patients, there are currently no approved drugs available that target motility of invasive cells, and only a handful of lead compounds are being tested in Phase I or II clinical trials. In the absence of effective drugs, early detection/diagnosis of metastasis becomes a critical element in the ongoing battle against cancer. This application aims to develop a conceptually novel technological platform with which to correlate motility and/or cytoskeletal dynamics of cancer cells to their metastatic potentials. Specifically, a combination of micro/nanotechnology, surface chemistry and cell and cancer biology will be used to prepare materials and systems with which to (i) create populations of micropatterned, """"""""designer"""""""" cells of desired shapes and (ii) elicit specific cell phenotypes. The micropatterns will be used to probe and distinguish metastatic from non-metastatic cancer cells based on their differential abilities to polarize and/or to rearrange cytoskeletal organization/dynamics in response to the applied geometries. Statistics over populations of designer cells will then provide analytical measures of the cells'invasiveness. The assays thus developed will be tested with cells from cell lines as well as those from cancer patients. Multiplexing the assays with microfluidics will allow for screening many samples/substances on one micropatterned """"""""chip"""""""". It is expected that the proposed systems will be more robust and accurate than the existing measures of invasiveness, such as counts of circulating cells or mRNA expression microarrays. The long term goal of this work is to develop the technology from the proof-of-concept experiments to clinical applications, where it would help save lives of cancer patients.
Given the lack of efficient medications/treatments against metastatic form of cancer and the fact that metastasis remains the major cause of death in cancer patients, accurate and early assessment/diagnosis of tumor's metastatic potential is the key to timely and efficient medical intervention. The work we propose will result in the development of a new class of microsystems that allow for such early diagnosis from the characteristic signatures of cancer cells immobilized on appropriately tailored microislands. By controlling cell shapes, the microislands will elicit specific behaviors/phenotypes of the cells such as to reveal their metastatic potential.
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