Why do cancer cells metastasize into particular organs?

Abstract

Metastatic spread of tumor cells is one of the most common causes of death in cancer patients. Therefore, elucidation of the molecular mechanisms that underlie the formation of metastatic colonies has been one of the major objectives of cancer research during the last two decades. In this review we will mainly discuss the mechanisms that cause a malignant cell to grow at a given site rather than at other possible sites, taking into account experimental and clinical evidence published on the subject. As a whole this evidence tends to confirm the hypothesis that organ-specific colonization by malignant cells often follows very specific and close interactions between the cancer cell and the target organ, either in terms of specific cellular adhesion or growth promotion. In this paper we would like to underscore the fact that cellular adhesion, either specific or unspecific, is a necessary but, by itself, insufficient condition for the development of metastases. It is the ability of the tumor cells to grow at the site where they arrested that ultimately determines whether a metastatic colony develops or fails to develop at that site.

Stromelysin-3 expression promotes tumor take in nude mice.

“…Indeed, S.C. injected cells mimic metastatic cells after extravasation, when these cells have to successfully implant at the metastatic site before being able to proliferate and invade (45,46). This process is dependent upon the cells' capability to survive in host tissues, either in an independent manner or by the recruitment of required factors from their near vicinity.…”

The Tumor Suppressor Smad4 Is Required for Transforming Growth Factor β–Induced Epithelial to Mesenchymal Transition and Bone Metastasis of Breast Cancer Cells

“…Whereas breast cancer has a predilection for the skeleton, uveal melanoma and colon cancer preferentially spread to liver (reviewed in refs. 23,24), indicating that additional factors are present in the tumor microenvironment that contribute to this process (25). TGF-h may be one of the crucial factors driving bone metastasis of breast cancer cells.…”

Inhibition of osteolytic bone metastasis of breast cancer by combined treatment with the bisphosphonate ibandronate and tissue inhibitor of the matrix metalloproteinase-2.

“…In most cases, cancer shows a selective nonrandom pattern of metastasis to particular organs, depending on the site where the primary tumor occurs (3,4). Breast cancer is known to have a strong predilection for spreading to bone (5)(6)(7)(8).…”