"What is it that decides what organs shall suffer a case of disseminated cancer?" asked London surgeon John Paget, exploring the deadly phenomenon of tumor metastasis in an 1889 edition of the journal Lancet. Cancer cells could spread with equal ease to any part of the body, he speculated, yet metastatic colonies seemed to favor certain organs, such as the lungs and liver. Paget imagined that the malignant cells might be like plant seeds that are carried by the winds in all directions but "can only live and grow if they fall on congenial soil."

To this day, scientists are trying to understand whether properties of the "seeds" or the "soil" determine where spreading tumors take root, and growing evidence suggests that both play important roles. Researchers in Japan have recently added intriguing details to that theory in a study that reveals how distant tumor cells interact with future sites of metastasis in the lungs through a signaling mechanism involved in immune responses to pathogens. The participation of this pathway may also offer a clue as to why certain organs seem more susceptible to metastases than others, according to senior author Yoshiro Maru of Tokyo Women's Medical University. "The lung is sensitive to microbes; it is a first defense," Maru explains. "So any stress, including the presence of cancer, might be recognized by organs responsible for host defense mechanisms. That is our guess."