The biology of melanoma brain metastasis

Brain metastases are clinically diagnosed in the majority of patients with metastatic melanoma. The prognosis for patients with melanoma brain metasta sis is poor with a median survival time of 6 months after diagnosis. Develo pment of better therapies requires a better understanding of the biology of melanoma brain metastasis. The development of a relevant in vivo model off ers this possibility. The intracarotid injection of different murine or hum an melanoma cells into syngeneic or nude mice produces metastases in differ ent regions of the brain. This site-specific metastasis is not due to patte rns of initial cell arrest, motility, or invasiveness, but rather to the ab ility of melanoma cells to proliferate in the brain parenchyma or the menin ges. The blood-brain barrier is intact in metastases that are smaller than 0.25 mm in diameter. Although in larger metastases the blood-brain barrier is leaky, the lesions are resistant to many chemotherapeutic drugs. We have also analyzed the malignant behavior of several melanoma cell lines isolat ed from brain or visceral metastases of patients. The cells from brain meta stases showed a slower growth rate and exhibited lower metastatic potential than cells from visceral metastases, indicating that brain metastases do n ot necessarily represent the end stage in the metastatic cascade. Rather, b rain metastases are likely to originate from a unique subpopulation of cell s within the primary neoplasm.