Abstract 890: Effects of Lewis lung carcinoma on trabecular microstructural changes in wild-type and plasminogen activator inhibitor-1 deficient mice fed a high-fat diet

Abstract

Abstract Bone is a major target organ of metastasis. The present study investigated the effects of Lewis lung carcinoma (LLC) on trabecular microstructural changes, using tomographic analysis, in distal femur and lumbar 4 vertebra from LLC-bearing wild-type and plasminogen activator inhibitor-1 (PAI-1) deficient mice (C57BL/6J background) fed the AIN93G diet or a high-fat diet; a group of AIN93G-fed non-tumor-bearing wild-type mice were used as controls. Compared to AIN93G-fed non-tumor-bearing wild-type mice, LLC significantly reduced bone volume fraction (BV/TV), connective density (Conn.D), trabecular number (Tb.N), trabecular thickness (Tb.Th) and bone mineral density (BMD) and significantly increased trabecular separation (Tb.Sp) in distal femurs of AIN93G-fed wild-type mice. In high-fat diet-fed mice, compared to the AIN93G-fed ones, LLC resulted in significantly greater reductions BV/TV, Conn.D, Tb.N and BMD and significantly greater increases in structure model index (SMI) and Tb.Sp. Deficiency in PAI-1, compared to wild-type mice, significantly increased BV/TV, Conn.D, Tb.N and significantly reduced SMI. In vertebra, LLC resulted in similar trabecular changes compared to the non-tumor-bearing wild-type controls, the high-fat diet reduced BV/TV and BMD and increased SMI, whereas PAI-1 deficiency did not affect trabecular microstructure in vertebrae. These results demonstrated (1) that LLC is detrimental to trabecular bone which may make it more vulnerable to malignant invasion, (2) that high-fat diet enhances LLC-induced trabecular deterioration and (3) that the improvement in trabecular microstructure by PAI-1 deficiency indicates that PAI-1 may play a role in trabecular microarchitectural deterioration during malignant progression. Citation Format: Lin Yan. Effects of Lewis lung carcinoma on trabecular microstructural changes in wild-type and plasminogen activator inhibitor-1 deficient mice fed a high-fat diet. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 890. doi:10.1158/1538-7445.AM2015-890