Intercellular crosstalk between CSCs and stromal cells or non-CSCs may cooperatively or competitively promote tumor aggressiveness and therapy resistance. Our work has identified 1, contribution of extracellular vesicle mediated signals to tumor progression, and 2, gain of vascular endothelial cell-like phenotype of CSCs by transdifferentiation. These studies have shed new light on tumor cell heterogeneity and potential innovative therapeutic approaches toward brain cancers.
a. Extracellular vesicles modulate the glioblastoma microenvironment via a tumor suppression signaling network directed by miR-1. Bronisz A, Wang Y, Nowicki MO, Peruzzi P, Ansari KI, Ogawa D, Balaj L, De Rienzo G, Mineo M, Nakano I, Ostrowski MC, Hochberg F, Weissleder R, Lawler SE, Chiocca EA, Godlewski J. Cancer Res. 2014 Feb 1;74(3):738-50. doi: 10.1158/0008-5472.CAN-13-2650. PMID: 24310399
b. Maintenance of the glioblastoma cellular hierarchy is regulated by junctional adhesion molecule-A. Lathia JD, Li M, Sathyan P, Hale J, Zinn P, Gallagher J, Wu Q, Sinyuk M, Nakano I, McLendon RE, Sloan AE, Carson C, Naik U, Hjelmeland AB, Majumder S, Rich JN, Cell Reports 2014 Jan 16;6(1):117-29. doi: 10.1016/j.celrep.2013.11.043. PMID: 24373972
c. Tumoral RANKL activates astrocytes that promote glioma cell invasion through cytokine signaling.Kim JK, Jin X, Sohn YW, Jin X, Jeon HY, Kim EJ, Ham SW, Jeon HM, Chang SY, Oh SY, Yin J, Kim SH, Park JB, Nakano I, Kim H. Cancer Lett. 2014 Oct 28;353(2):194-200. doi: 10.1016/j.canlet.2014.07.034. Epub 2014 Jul 28. PMID: 25079688
d. Crosstalk between glioma initiating cells and endothelial cells drives tumor progression. Jeon HM, Kim SH, Park JB, Kim SH, Nakano I, Kim H. Cancer Res. 2014 Aug 15;74(16):4482-92.
e. The LIM-only transcription factor LMO2 determines tumorigenic and angiogenic traits in brain cancers. Kim SH, Oh SY, Jin X, Kim EJ, Jeon HM, Beck S, Jin X, Kim JK, Park CG, Chang SY, Yin J, Kim T, Jeon YJ, Song J, Lim YC, Nakano I (co-Corresponding Author), and Kim H. Cell Death and Differentiation 2015 [in press]