The Cellular Basis for Prostate Cancer Metastasis

Abstract

It has been known for over 100 years that tumors originating in different locations metastasize to different sites. Examples include the metastasis of clear cell carcinoma of the kidney to the thyroid; small cell carcinoma of the lung to brain, cutaneous melanoma to skin, liver, brain and bowel, and ocular melanoma from the eye specifically to the liver. Many other examples are known, yet the mechanism behind site-specific tumor metastasis has been under dispute for many decades. Paget’s theory, originally formulated in 1888, [1] maintained that tumors colonized particular organs because they grew there preferentially. In a lasting analogy, he compared the tumor to a seed and the organs to the soil. He maintained that tumors would preferentially colonize only those organs that had congenial soil, a theory now know as the “seed and soil” hypothesis of tumor metastasis. In contrast, the surgeon Ewing argued that tumors merely followed the vascular circulation and colonized the first organ that they encountered downstream from the primary tumor [2]. Since many tumors shed into the venous circulation, the first organ downstream would be the lung, and Ewing maintained that this would explain the preference of many metastatic tumors for the lung. With hindsight, we now know that both Paget and Ewing were partially correct.