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We propose that hyaluronate, a major component of extracellular matrices through which cells migrate during embryonic tissue development and in regenerative processes, is also concentrated in the environment through which neoplastic cells invade local host tissues and may facilitate this process. The hyaluronate content of invasive V2 carcinoma grown in rabbit was found to be 3-4 times greater than that of the same tumor grown in the nude mouse, in which it is noninvasive. Moreover, hyaluronate concentrations were most elevated in the connective tissue interface between the tumor mass and the neighboring host tissue in the invasive rabbit tumors. The particular site of tumor implantation in the rabbit or nude mouse did not affect the concentrations of hyaluronate in either the parenchyma or the surrounding connective tissue. Similar values were obtained for neoplasms grown in muscle, which normally contains little hyaluronate, and in subcutaneous tissue, which is relatively rich in this glycosaminoglycan.

Thymosin beta 4, recently isolated from calf thymus, is present in a number of rat and mouse tissues, including spleen, thymus, brain, lung, liver, and heart muscle. High concentrations are found in peritoneal macrophages, suggesting that its occurrence in other tissues may be related to the presence of macrophages or macrophage-like cells in these tissues. The conclusion that "thymosin" beta 4 does not originate solely in the thymus gland is supported by the high concentrations found in tissues of athymic (nu/nu) mice.

A human mucinous cystadenocarcinoma of the ovary was propagated in nude mice. After cryopreservation of the 3rd-passage xenograft for 4 years, subsequent in vivo transplants showed the emergence of two distinct populations, one resembling the original human adenocarcinoma and the other resembling a spindle-cell sarcoma. These two tumor cell populations were confirmed to be human and murine, respectively, by cytogenetic study, and the epithelial tumor cells were further shown to be of human origin by immunoperoxidase staining of blood group A antigen. Separation of the two tumor cell populations in vitro permitted the independent propagation of the human and murine tumor cells in vitro and in vivo. The murine sarcoma was also capable of growth in ordinary BALB/c mice. These results indicate that human cancer cells can induce malignancy in adjacent, putatively normal, cells of nude mice in vivo.