Fig. 4

Specific human melanoma BM cells induce BBB compromise without contributions of immune cells in vitro. a TEER was measured as a surrogate for inter-endothelial tight junction integrity in an in vitro BBB model. A significant decrease in TEER was found in a cerebrotropic human melanoma daughter cell line (A375Br), derived by repeated intra-carotid injection of A375P parental cells and expansion of cells isolated from the brain. A375P cells derived from a metastatic lymph node increased TEER. Short-term melanoma cultures from other extracerebral sites (YUCOT, YUSIT, and YUVON) similarly did not result in decreased resistance compared to CTRL (HUVEC and astrocytes co-cultured without the addition of melanoma cells). b A panel of short-term cultures derived from human melanoma BMs was similarly studied and TEER changes determined. Co-culture with some but not all melanoma BMs resulted in decreased resistance compared to CTRL. c TEER changes were compared to MRI-based tumor and edema volume measurements of resected lesions from which the cultures were derived. Black circles represent cell lines with decreased TEER, whereas white circles correspond to cell lines with increased TEER changes. d Four of the nine cell cultures that decreased TEER (black circles) are from more edematous tumors, whereas all the cell cultures that did not decrease TEER (white circles) were from less edematous tumors