Abstract
Conclusions
In the present minireview we have discussed several types of model systems which have given valuable clues to the ways in which leukemia and lymphoma cells mediate organ specific metastasis. Most patent is that these types of malignancies probably utilize normal receptor-mediated mechanisms for organ specific recognition. The animal models which have been most extensively studied indicate that the following three recognition mechanisms can be employed by metastatic lymphoma variants:
(1) Normal organ cells have receptors for determinants on metastatic variants 17
(2) metastatic variants have receptors for determinants expressed on endothelial cells 2 , 19 ; and
(3) an undefined interaction occurs between normal organ cells and metastatic variants 16 .
A great deal of evidence suggests that organ specific metastasis is at least partially mediated through carbohydrate determinants which are recognized by receptors. It is possible that these receptors may be part of a larger family of recognition molecules which mediate normal cell-cell interactions. Despite this, a role for a “microenvironmental” mechanism cannot be ruled out and, indeed, is not mutually exclusive of the receptor-mediated adherence mechanism. In fact, in our bone marrow model our preliminary results suggest the existence of growth factors which are secreted by adherent bone marrow cells and which strongly stimulate the growth of the leukemia cell lines. Nevertheless, the avid binding of leukemia cells to the adherent cells of the bone marrow appears to be an important mechanism whereby leukemia cells are “held” in the bone marrow. The continued development of MAbs which recognize organ specific receptors on tumor cells, the isolation of these receptors, and their molecular biology should reveal whether a multigene family for organ specific recognition exists. These receptors will serve as functional markers in contrast to conventional markers such as T- and B-cell determinants. While it is true that T- and B-cell markers may indicate the probable cell lineage of the transformant, they do not, for example, explain why ALL grows in the bone marrow and not in the spleen. We suggest that the identification of “homing” receptors using MAbs will, for the first time, enable us to gauge the status of a malignancy, accurately determine the prognosis, and even allow us to choose the appropriate MAb to be used for the therapy of individual leukemias.
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