Elevated Serum Periostin Levels in Patients with Bone Metastases from Breast but not Lung Cancer

Abstract

Periostin is a recently identified gene that is preferentially expressed in periosteum, indicating a potential role in bone formation and maintenance of structure. We independently identified and isolated periostin from cancer tissue, using the palindromic PCR-driven cDNA Differential Display technique. For the present work, we developed a novel sandwich chemiluminescence assay to detect serum periostin level using newly developed monoclonal and polyclonal antibodies. We investigated serum periostin levels in breast cancer and small cell lung cancer patients, especially in patients with bone metastasis. The study included 58 breast cancer and 44 small cell lung cancer patients. Serum periostin levels were elevated in breast cancer patients presenting with bone metastases (92.0 +/- 28.6 ng/ml) compared to similar breast cancer patients without evidence of bone metastasis (55.0 +/- 16.6 ng/ml, p = 0.04). No correlation was found between the serum periostin level and any other prognostic factors, such as clinical stage and lymph node metastasis in breast cancer. Serum periostin levels thus appear to serve as a marker of bone metastasis from breast cancer. In contrast, serum periostin levels were similar in samples from patients with small cell lung cancer who did or did not have bone metastasis. However, increasing T-stage and N-stage of patients with small cell lung cancer were correlated with higher periostin levels (T4, 126.5 +/- 29.7 ng/ml v.s. T2, 64.9 +/- 16.1 ng/ml, p = 0.03; and T4 v.s. T1, 36.3+/- 7.5 ng/ml, p = 0.01; N3, 108.7 +/- 17.3 ng/ml v.s. N2, 49.7+/- 10.9 ng/ml, p = 0.01). Periostin has a substantial homology with the insect cell adhesion molecule, fasciclin I. Thus, expression of periostin may facilitate tumor cell adhesion to the bone surface. In fact, we found by in situ RNA hybridization, that the periostin gene was highly expressed in the stromal cells immediately surrounding the tumor, but not within the breast cancer cells themselves.

Proteomic Analysis of Differentially Expressed Proteins in Peripheral Cholangiocarcinoma

“…Periostin has been shown to induce cell migration and also epithelial-mesenchymal transition in pancreatic cancer cells [43], thus it may represent a novel mediator of tumor growth in cholangiocarcinoma. In addition, periostin has been reported to be elevated in serum of some patients with cancers including thymoma and non-small cell lung carcinoma [44]. The detection of periostin or other overexpressed proteins such as 14-3-3 preoteins in serum may therefore prove to be useful markers for detection of malignancy.…”

Periostin, secreted from stromal cells, has biphasic effect on cell migration and correlates with the epithelial to mesenchymal transition of human pancreatic cancer cells

“…31 These reports suggested that periostin is involved in tumor spread, invasion and metastasis. At the molecular level, periostin activated the Akt/PKB signaling pathway 11 through avb3 9 or b4 12 integrins to increase cell survival.…”

N-glycoprotein profiling of lung adenocarcinoma pleural effusions by shotgun proteomics

“…Periostin is a marker for metastatic lung and breast cancers, 13,16 and promotes invasion and metastatic growth in head and neck, 17 pancreatic, 18 and colon cancer, 19 and acts on the crosstalk between a m b 5 integrins and the EGF-receptor. 20,21 This protein is actually 1 of the most promising biomarkers, as its upregulation depends on the formation of desmoplastic stroma.…”