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Presence of a Growth-stimulating Factor in Serum following Primary Tumor Removal in Mice¹

University of Pittsburgh, Pittsburgh, Pennsylvania 15261

The effect of removal of a primary tumor on the kinetics of cells in a metastasis was evaluated using six different tumors (C3H, MXT_a, MXT_b, MC54, CD8, and 3LL) which varied relative to their origin, histology, and the strain of mice in which they were carried. There was an increase in the labeling index (LI) of a distant tumor focus ("metastasis") associated with the removal of each of the tumor types and unrelated to operative and anesthetic trauma. Information presented supports the presence of a serum growth factor as being responsible for the phenomenon. Serum obtained from mice following removal of a tumor, when transferred to a recipient with the same type of tumor as in the donor, resulted in an increase in the LI of the tumor. Multiple injections of serum failed to add to the increase but did prolong its presence, suggesting that there is a finite population of cells, most likely in the G₁-G₀ phase, which are capable of responding to the stimulating factor.

The transfer of serum obtained following removal of a tumor type different from that in recipients resulted in findings which indicate that tumors producing a stimulating growth factor are those capable of responding to it. Serum obtained from animals with unremoved tumors or less than 18 h after removal failed to substantially augment the LI of tumors in recipients. It is postulated that the growth factor released by a tumor is in an inactive form which becomes activated over time.

Observations indicate that medium conditioned by the growth of C3H tumor contains a growth-stimulating factor which is capable of increasing the LI of a C3H tumor in a recipient in a fashion similar to that obtained following tumor removal. That finding indicates the capability of the tumor to elaborate growth-stimulating material which may be similar to that found in serum.

The findings presented refute the premise that removal of a primary tumor is a local phenomenon with no other biological consequences. They indicate that, following primary tumor removal, metastatic behavior may be affected by an interplay of growth factor(s) which can influence the outcome of a host to its tumor.

¹ This investigation was supported in part by a USPHS Grant R01-CA-14972 awarded by the National Cancer Institute, Department of Health and Human Services.

² To whom requests for reprints should be addressed, at Room 914, Scaife Hall, 3550 Terrace Street, Pittsburgh, PA 15261.

Received 8/15/88. Revised 12/21/88. Accepted 1/13/89.

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