Expression of CD44, a transmembrane glycoprotein involved in cell-cell and cell-matrix interactions, has been associated with growth and metastatic behavior in several malignant tumors. In contrast to most other malignancies, in which up-regulation of CD44 is related to tumor progression, the absence of CD44 expression characterizes the aggressiveness of neuroblastomas in clinical studies. In this study, cells of human neuroblastoma cell lines (IMR-32, Kelly, LAN-1, LAN-5, LS, SH-SY5Y and SK-N-SH) were injected subcutaneously into SCID mice, and their growth behavior and CD44 expression were analyzed. All neuroblastoma cells engrafted in the SCID mouse, but primary tumor growth and metastatic potential varied considerably. Expression of CD44 was associated with a metastatic pattern of the neuroblastoma cell lines. CD44-positive neuroblastomas produced multicellular metastases predominantly located in the intra- and periarterial space of the lung. CD44-negative neuroblastomas developed numerous micrometastases in the lung interstitium. In conclusion, the entire spectrum of metastatic patterns can be modeled in SCID mice using the human neuroblastoma cell lines employed in this study. Our xenograft model provides a platform for investigating the complex processes involved in metastasis formation and for testing new anti-metastatic drugs. In particular, the role of CD44 in the formation of metastasis can be evaluated.
