Hypercalcemia associated with malignancy is most often mediated by:

PTHrp was discovered as a product of human cancers that are of squamous cell origin and that are associated with hypercalcemia. However, normal tissues also express this protein - skin keratinocytes, lactating mammary epithelium, placenta, and fetal parathyroid glands. The gene for PTHrp and for PTH is on paired chromosomes. PTHrp binds to PTH receptor; it exhibits most of the actions of PTH on bone and kidney. Hence, it produces hypercalcemia. One action of PTH NOT shared by PTHrp is: stimulation of renal 1-hydroxylase. Hence, patients with hypercalcemia caused by PTHrp do not have elevated 1,25-dihydroxycholecalciferol. The most impoant physiological role of PTHrp is regulation of endochondral bone formation .