ABSTRACT
Actually, the concept that tumors are heterogeneous is not new. Paget (12) analyzed the postmortem data of women who died of cancer and noticed the high frequency of metastasis to the ovaries and different incidence of skeletal metastases associated with different primary tumors. Paget concluded that the organ distribution of metastases is not a matter of chance and suggest that metastases develop only when the ‘‘seed’’ (certain tumor cells with metastatic ability) and the ‘‘soil’’ (colonized organs providing a microenvironment for growth advantage) are compatible. In recent years, Paget’s hypothesis has received considerable experimental and clinical support (13-16). A current definition of the ‘‘seed and soil’’ hypothesis encompasses three principles. First, neoplasms are biologically heterogeneous (1,13). Second, the process of metastasis is highly selective, favoring the survival and growth of a small subpopulation of cells that pre-exist in the parent neoplasm (17). Third, the outcome of metastasis depends on multiple interactions of metastatic cells with homeostatic mechanisms. The majority of malignant tumors actually usurp
homeostatic mechanism to gain growth advantage. Neoplastic angiogenesis is an excellent example.
