Brain Metastasis Cell Lines Panel: A Public Resource of Organotropic Cell Lines

Abstract

Spread of cancer to the brain remains an unmet clinical need in spite of the increasing number of cases among patients with lung, breast cancer, and melanoma most notably. Although research on brain metastasis was considered a minor aspect in the past due to its untreatable nature and invariable lethality, nowadays, limited but encouraging examples have questioned this statement, making it more attractive for basic and clinical researchers. Evidences of its own biological identity (i.e., specific microenvironment) and particular therapeutic requirements (i.e., presence of blood-brain barrier, blood-tumor barrier, molecular differences with the primary tumor) are thought to be critical aspects that must be functionally exploited using preclinical models. We present the coordinated effort of 19 laboratories to compile comprehensive information related to brain metastasis experimental models. Each laboratory has provided details on the cancer cell lines they have generated or characterized as being capable of forming metastatic colonies in the brain, as well as principle methodologies of brain metastasis research. The Brain Metastasis Cell Lines Panel (BrMPanel) represents the first of its class and includes information about the cell line, how tropism to the brain was established, and the behavior of each model in vivo. These and other aspects described are intended to assist investigators in choosing the most suitable cell line for research on brain metastasis. The main goal of this effort is to facilitate research on this unmet clinical need, to improve models through a collaborative environment, and to promote the exchange of information on these valuable resources.

Figure 1.. Cancer cell lines in the BrMPanel.

Brain metastatic (BrM) cell lines have been established from human or mice parental cells (derived from primary tumors, pleural fluids or lymph node metastasis). Depending on the model, some cell lines were labelled with fluorescent (i.e. GFP) and/or bioluminescent (Luc) reporters and they underwent subsequent in vivo selection, for 0–5 rounds. Alternatively, spontaneous metastasis obtained from patients or mice (i.e. derived from genetically engineered mouse models (GEMM) or orthotopic injections) could be a direct source of BrM cell lines, without the need of performing in vivo selection. The BrMPanel has 60 cell lines from breast cancer (38 cell lines, 63.3%), lung cancer (8 cell lines, 13.3%) and melanoma (14 cell lines, 23.3%) of human (h), mouse (m), or rat (r) origins. Molecular drivers and cancer subtypes are represented for each cancer type: Breast cancer: 16 entries of HER2+, 42.1%; 19 entries of triple-negative breast cancer patients (TNBC), 50.0%; 3 entries of other, 7.9%; Lung cancer: KRAS mutant and p53 null (1 out of 8 cell lines of 12.5%) or EGFR alterations (3 out of 8 cell lines, 37.5%); Melanoma: 8 BRAF mutant cell lines (57.1%) and 3 Ret alterations (21.4%). Analysis of the molecular profiles correspond to the parental cell lines.