Mechanical loading promotes Lewis lung cancer cell growth through periostin

Abstract

Mechanical loading is known to trigger proliferation of tumor cells. Periostin is a new molecule found to increase in many cancers. To determine how mechanical strain modulates tumor growth and its possible mediation by periostin through TGF-beta1, Lewis lung cancer cells were cultured on flexible-bottomed culture plates and cyclically strained using Flexercell Strain Unit. Real-time RT-PCR was used to quantify periostin and TGF-beta1 mRNA levels at 6, 12, 18, and 24 h of loading. In addition, periostin and TGF-beta1 neutralizing antibodies were added to the medium. We showed that the proliferative ability of Lewis cancer cells was significantly increased by cyclical strain. This change can be blocked by 5 microg/ml of periostin neutralizing antibody. Periostin mRNA increased by 1.1-, 3.2-, 4.7-, and 9.2-fold while TGF-beta1 mRNA increased by 5.3-, 10.3-, 7.1-, and 6.5-fold at 6, 12, 18, and 24 h, respectively. Periostin protein in medium increased after cyclical strain. Expression of periostin mRNA in response to mechanical loading was completely blocked by 2.5 microg/ml of TGF-beta1 neutralizing antibody. In addition, overexpression of periostin in Lewis cells can promote cell proliferation. Our results suggest that periostin is a potent positive regulator of tumor growth in response to mechanical loading and is possibly a downstream factor of TGF-beta1.

Influence of IL13 on Periostin Secretion by Synoviocytes in Osteoarthritis

“…Periostin clearly plays crucial roles in tissue repair. However, in some cases, chronic or superabundant periostin expression can accelerate pathogenesis of tumours (22,23), bronchial asthma (24,25), atopic dermatitis (26,27), polycystic kidney disease, and other fibrotic diseases (28). As recently reported, periostin promotes chronic inflammation by activating nuclear factor kappa B (NF-ĸB) signaling (26,29,30).…”

The multiple facets of periostin in bone metabolism

“…In summary, these data show that periostin is a prosurvival protein, largely involved in cell response to environmental stress [61,63,68]. By binding to integrins or cell surface receptors, periostin can activate intracellular signaling pathways leading to inhibition of apoptosis through inactivation of caspases 3 and 9 and prosurvival signaling resulting in increased bone formation [12,61,66,73].…”

“…By binding to integrins or cell surface receptors, periostin can activate intracellular signaling pathways leading to inhibition of apoptosis through inactivation of caspases 3 and 9 and prosurvival signaling resulting in increased bone formation [12,61,66,73].…”

Zoledronate Effects on Systemic and Jaw Osteopenias in Ovariectomized Periostin-Deficient Mice

“…We previously reported that loading and PTH increases periostin expression in osteocytes [34], and that periostin decreases the expression of apoptotic molecules such as caspase 3 [47], potentially through direct binding to intergrin αVβ5 which activate downstream FAK and Akt pathways. In others tissues, increased periostin expression have also been suggested to represent an adaptative cell response to maintain cell survivals against an environmental stress [69], [70], [71]. Therefore, it is possible that absence of periostin promoted BPs pro-apoptotic effects on osteocytes [61]–[62], which together with low bone turnover would explain the persistence and accumulation of empty osteocytic lacunae.…”