BLOC1S3 and neoplasm: The following two theories have been proposed by Meuten, in 1981, to explain why not all dogs with AGASACA develop hypercalcemia: the first is that PTH-rp is produced by well-differentiated cells, therefore, if the tumor is highly undifferentiated, it may not have functional cells to synthesize the peptide; the second explanation is that a large number of cells are required to produce enough PTH-rp to interfere with normal calcium metabolism; therefore, only larger tumors can cause hypercalcemia [11].