Toward a noninvasive measurement of cancer stem cells and tumor aggressiveness
Brown SL, Elmghirbi R, Nagaraja T, Keenan KA, Lapanowski K, Panda S, Inder P, Cabral G, Liu L, Kim JH, Movsas B, Chetty IJ, Ewing JR, Parry R. Toward a noninvasive measurement of cancer stem cells and tumor aggressiveness. Int J Radiat Oncol Biol Phys. Oct 1 2016;96(2s):E592.
Int J Radiat Oncol Biol Phys
Purpose/Objective(s): The purpose of this study was to explore the relationship between tumor interstitial fluid pressure, which has historically been used as ameasure of tumor aggressiveness, and expression ofCD44, a marker of cancer stem cells. Cancer stemcells (CSCs) are a subpopulation of tumor cells that express specific proteins that putatively confer an aggressive proliferative, invasive, and metastatic phenotype such that CSCs have the ability to initiate the regrowth of a tumor. One accepted marker ofCSCs is CD44, the receptor for hyaluronic acid (HA). CD44 has been shown to be overexpressed in several cancers, including primary cancers from breast, prostate, lung, pancreas, brain, and from metastatic brain tumors. Tumor aggressiveness has been historically measured invasively using tumorinterstitial fluid pressure (TIFP). It has been demonstrated theoretically that TIFP can be measured non-invasively using contrast enhance magnetic resonance imaging (CE-MRI). Recently, it was demonstrated experimentally that both interstitial fluid flux and tissue porosity could be estimated by CE-MRI, thus potentially leading to the development of a non-invasive estimate of TIFP. The objectives of the study were to further validate CE-MRI as a noninvasive tool to measure tumoraggressiveness by determining the correlation between CD44 expression and a non-invasive MRI TIFP measurement. Materials/Methods: Transplanted U251 human glioblastomas were grown intracranially in nine athymic rats.When the tumors reached between 3 and 6 mminmaximumdiameter, TIFP wasmeasured non-invasively usingCE-MRI. TIFP was measured in units of mmHg. At the completion of the TIFP measurement, tumors were excised, formalin fixed and processed for CD44 expression. CD44 was semi-quantitatively scored following the procedure ofthe Allred IHC scoring system. Results: There was apositive significant correlation between CD44 expression and the non-invasive MRI TIFP measurement (R squared Z 0.68). A possible explanation is that CD44 is upregulated in response to increased physical stress as a consequence of the high TIFP. Conclusion: The two parameters, TIFP and CD44 were directly and positively correlated. The predictive value of TIFP to measure CD44 expression should be further explored. Future work will incorporate other tumor types and response to therapies, especially radiation therapy.