Description
Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths (Jemal et al. 2008 ). While most primary tumors can be resected surgically, CRC frequently metastasizes to the liver, which is responsible for the high mortality of the disease (Christofori 2006 ). To achieve metastasis, cancer cells need to invade surrounding tissues, penetrate microvessels, survive in circulation, disseminate to distant organs, form micrometastases, and expand into macrometastases. To progress through these steps, tumor cells often acquire the capability of survival and invasion by activating metastatic signaling pathways or inactivating metastasis suppressor genes (Christofori 2006 ; Smith and Theodorescu 2009 ). In addition to these cell- autonomous changes, the tumor stroma, including bone marrow-derived myeloid cells, actively participate in early steps of the metastatic cascade in some mouse models (Joyce and Pollard 2009 ). For example, tumor-associated macrophages (TAMs) promote migration and intravasation of mammary tumor cells (Goswami et al. 2005 ; Wyckoff et al. 2007 ). Bone marrow-derived cells that express myeloid cell marker CD11b and granulocyte marker Gr-1 also promote metastasis of breast cancer cells, likely through promotion of intravasation and suppression of immune responses (Yang et al. 2008 ). These reports suggest that bone marrow-derived myeloid cells can help cancer epithelium in early steps of metastasis. It remains to be determined whether therapeutic targeting of such myeloid cells can prevent can-cer metastasis (Gadea and Joyce 2006 ).
As a model for invasive CRC, we previously constructed cis-Apc +/Δ716 Smad4 +/− ( Apc/Smad4 ) mice that develop intestinal adenocarcinomas with marked invasions thorough biallelic loss of Apc and Smad4 tumor suppressor genes in the intestinal epithelium (Takaku et al. 1998 ; Taketo and Edelmann 2009 ). In the Apc/Smad4 tumors, we reported that the invading cancer epithelium is associated with immature myeloid cells (iMCs), and that the iMCs promote CRC invasion into the adjacent tissues (Kitamura et al. 2007 ). Here we have used a transplantation model to deter-mine whether CRC cells can recruit the iMCs in the metastasizing sites. This is an excerpt from the results published recently in (Kitamura et al. 2010 ).