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Cancer Metastasis Rev (2007) 26:705715
DOI 10.1007/s10555-007-9088-5
Metastasis: the seed and soil theory gains identity
Emmanouil Fokas & Rita Engenhart-Cabillic &
Kiriakos Daniilidis & Frank Rose & Han-Xiang An
Published online: 5 September 2007 # Springer Science + Business Media, LLC 2007
Abstract The metastatic spread of tumor cells to distant sites represents the major cause of cancer-related deaths. Cancer metastasis involves a series of complex interactions between tumor cells and microenvironment that influence its biological effectiveness and facilitate tumor cell arrest to distant organs. More than a century since Paget developed the theory of seed and soil, the enigma of tissue specificity observed in metastatic colonization of tumor cells begins to unfold itself. The advent of new technologies has led to the discovery of novel molecules and pathways that confer metastasis-associated properties to the cancer cells, mediating organ specificity and unique genetic signatures have been developed using micro-array studies. Future clinical studies and new antimetastatic compounds aiming to improve survival of patients with metastasis will most probably be based on these signatures. This review summarizes the plethora of old and new molecules that are strongly correlated with organ-specific
metastases and which provide now an identity to the theory of seed and soil.
Keywords Organ-specific metastasis . Colonization . Seed and soil . Genetic signature
1 Introduction
Despite the significant improvement in both diagnostic and therapeutic modalities for the treatment of cancer patients, metastasis still consists the major cause of mortality being responsible for 90% of all cancer deaths [1]. Metastasis (Greek: the change in the state) is a complex phenomenon involving a series of complex biological events. Primary tumor cells continuously proliferate and their adherence to adjacent normal and abnormal cells as well as to basement membrane is decreased. Deadhesion and escape of malignant cells into blood or lymphatic vessels (intravasation) is followed by arrest through restriction in capillary beds of host tissue and exit from the circulation (extravasation). Subsequently, establishment of sufficient nutrient supply through neoangiogenesis and interaction with host stromal tissue is essential for formation of metastases. In the new environment, malignant cells will either remain in a dormant state for long time (dormant metastases) or continue to grow further [2, 3].
One particularly important issue, which has been remained unanswered for...