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Role of Host and Tumor Calcium in Metastases¹

Departments of Surgery and Pathology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213

To define more clearly the role of tumor and host calcium in the development of metastases, a series of in vivo investigations were conducted with Walker tumor which demonstrated the following:

(a) Tumor calcium was modified by the level of serum calcium in the host. A reduction of tumor calcium occurred when tumors were grown in animals whose serum calcium was <5.0 mg % and a marked increase of calcium was observed in tumors from animals with serum calcium >11.0 mg %. Transfer of successive generations of tumor in hypocalcemic animals (serum calcium 5.0–8.9 mg %) failed to significantly alter tumor calcium, whereas those transferred in hypercalcemic animals (>11.0 mg %) demonstrated a progressive elevation of calcium.

(b) Host serum calcium levels failed to influence the development of metastases. The incidence of liver and lung metastases was similar following the transfer of tumor cells into normo-, hypo-, and hypercalcemic animals.

(c) As determined by the disappearance of labeled tumor cells from their injection sites, there was no difference in the invasive characteristics of cells obtained from low or high calcium-containing tumors.

(d) Plugs removed from low and high calcium-containing tumors were inserted into the legs of hypo- and hypercalcemic animals which were either untouched until sacrifice or were subjected to hind-quarter amputation 7 or 12 days after implantation. In no circumstances was a difference in the incidence of lung metastases observed.

These studies and recent observations by others suggest that the role of calcium in the phenomenon of tumor metastasis requires further clarification.

¹ Aided by USPHS Grants CA-05716, CA-06949, CA-10663 and by American Cancer Society Grant P-142.

Received 11/17/67. Accepted 5/ 1/68.