Immune cells facilitate lung metastasis of breast cancer cells

Abstract

The Paget's ‘seed and soil’ metastasis theory is often simplistically assumed to consist of two components: cancer cells and the organ destination site that enables attachment and growth of recruited cancer cells. To analyse this theory, we have asked following questions: (1) Although chemokine receptors are often not detectable on cancer cells using conventional surface staining techniques, what is their role in metastasis; and (2) whether the recruitment/attachment of cancer cells alone at their metastatic site is sufficient to promote cancer growth. To study this, we have generated “natural” variants of highly metastatic murine breast cancer 4T1 cells using manipulations that do not introduce artificial features. The cells were depleted of chemokine receptor‐expressing subsets using chemokines fused with toxins (chemotoxins). We demonstrate that metastasis is mediated by a small subset of 4T1 cells (seed) that express a specific chemokine receptor. However, chemokine receptors alone and as well as the “soil” (the destination site) alone were not sufficient to promote tumor growth. Instead, it required the active participation of immune cells, indicating that the metastasis also requires a third player – “sun”. This work was supported by the Intramural Research Program of the National Institute on Aging, NIH.