Hypercalcemia in breast cancer

Abstract

Hypercalcemia is relatively frequent in malignancy with or without osteolytic bone metastases. It is thought that neoplastic cells may secrete substances which not only stimulate osteoclastic activity but are also capable of modifying the absorption, excretion, and resorption of calcium and phosphate ions. Since 1987, we have studied 24 breast cancer patients with hypercalcemia (22 with bone metastases and two without). The group of 22 patients with bone metastases were divided into two subgroups. The first consisted of 10 patients with high serum levels of humoral factors, such as parathyroid hormone-related protein (PTHrP), and/or prostaglandin E2 (PGE2) and/or interleukin 1 (IL-1), and high levels of bone markers, such as alkaline phosphatase, bone Gla protein and urinary hydroxyproline. The second subgroup consisted of 12 patients with high levels of bone markers alone. Bone histologic analysis showed an osteoclastic activation surrounding metastatic tumor tissue in six out of 10 patients of the first subgroup, while an evident osteolysis caused by the tumor cells was noted in seven out of 12 patients of the second subgroup. The two patients without bone metastases showed normal biochemistry and bone histologic examination. The authors, having tried to explain the pathogenesis of hypercalcemia, emphasize the importance of humoral factors secreted by tumor cells as a direct or indirect cause of hypercalcemia. The origin of hypercalcemia remains unclear in two patients without bone metastases.

Inhibition of Wilms' tumor growth by intramuscular administration of tissue inhibitor of metalloproteinases-4 plasmid DNA

“…Consistently, tumor cell invasion and metastasis can be inhibited by upregulation of TIMP expression (Imren et al, 1996;Khokha, 1994;Watanabe et al, 1996). In addition to inhibiting tumor cell invasion and metastasis, several previous studies have also demonstrated that overexpression of TIMPs inhibit primary tumor growth of several dierent cells including c-Ha-ras transfected rat embryo ®broblasts (Imren et al, 1996), murine B16 melanoma cells (Imren et al, 1996;Khokha, 1994), human M24net melanoma cells (Francini et al, 1993), and DDL-1 human colon carcinoma cells (Bian et al, 1996).…”

Expression of Heparanase by Primary Breast Tumors Promotes Bone Resorption in the Absence of Detectable Bone Metastases

“…In breast cancer, bone metastases frequently result in lytic lesions with numerous osteoclasts and areas of bone erosion immediately surrounding foci of metastatic tumor cells (45). The progression of osteolytic bone metastases requires the establishment of functional interactions between metastatic cancer cells and bone cells (24,46), which are presumably mediated by soluble stimulators of osteoclast activity (46,47). Our results show that established foci of tumor cells are not necessary for the stimulation of bone resorption and support the idea that bone resorption is induced by the release of a systemic osteoclast-stimulating factor(s) from tumor cells expressing high levels of heparanase.…”

In vivo study of the GC90/IRIV vaccine for immune response and autoimmunity into a novel humanised transgenic mouse

“…Parathyroid hormone-related protein (PTH-rP) is an attractive candidate as a target antigen in the protocol of active specific immunotherapy of prostate carcinoma and epithelial malignancy bone metastases. It was originally described as the factor responsible for humoral hypercalcaemia of malignancy (HHM) (Suva et al, 1987;Francini et al, 1993). It is expressed in 90% of prostate and (spindle-cell) lung cell carcinomas and 95% of bone metastases of epithelial cancers, and is produced in small amounts in normal adult tissues (Iguchi et al,…”