The tumor microenvironment can enhance the invasive capacity of tumor cells. We showed that expression of angiopoietin-like protein 2 (ANGPTL2) in osteosarcoma (OS) cell lines increased and the methylation of its promoter decreased with time when grown as xenografts in mice compared with culture. Compared with cells grown in normal culture conditions, the expression of genes encoding DNA demethylation-related enzymes increased in tumor cells implanted into mice or grown in hypoxic, serum-starved culture conditions. ANGPTL2 expression in OS cell lines correlated with increased tumor metastasis and decreased animal survival by promoting tumor cell intravasation mediated by the integrin α5β1, p38 mitogen-activated protein kinase, and matrix metalloproteinases. The tolloid-like 1 (TLL1) protease cleaved ANGPTL2 into fragments in vitro that did not enhance tumor progression when overexpressed in xenografts. Expression of TLL1 was weak in OS patient tumors, suggesting that ANGPTL2 may not be efficiently cleaved upon secretion from OS cells. These findings demonstrate that preventing ANGPTL2 signaling stimulated by the tumor microenvironment could inhibit tumor cell migration and metastasis.

The purpose of our study was to investigate whether quantitative diffusion-weighted images (DWI) were useful for monitoring the therapeutic response of primary bone tumors. We encountered 18 osteogenic and Ewing sarcomas. Magnetic resonance (MR) images were performed in all patients before and after therapy. We measured the apparent diffusion coefficient (ADC) values, contrast-to-noise ratio (CNR), and tumor volume of the bone tumors pre- and posttreatment. We determined change in ADC value, change in CNR on T2-weighted images (T2WI), change in CNR on gadopentetate dimeglumine (Gd)-T1-weighted images (Gd-T1WI), and change in tumor volume. The bone tumors were divided into two groups: group A was comprised of tumors with less than 90% necrosis after treatment and group B of tumors at least with 90%. Changes in ADC value, tumor volume, and CNR were compared between the groups. Change in the ADC value was statistically greater in group B than that in the group A (p = 0.003). There was no significant difference in the changes in CNR on T2WI (p = 0.683), in CNR on Gd-T1WI (p = 0.763), and tumor volume (p = 0.065). The ADC value on DWI is a promising tool for monitoring the therapeutic response of primary bone sarcomas.

The minimum ADC is useful for evaluating the chemotherapeutic response of osteosarcoma.

Purpose:To determine whether quantitative diffusionweighted imaging (DWI) is useful for characterizing poorly contrast-enhanced and T2-prolonged bone masses. Materials and Methods:We studied 20 bone masses that showed high signal intensity on T2-weighted images and poor enhancement on contrast-enhanced T1-weighted images. These included eight solitary bone cysts, five fibrous dysplasias, and seven chondrosarcomas. To analyze diffusion changes we calculated the apparent diffusion coefficient (ADC) for each lesion. Results:The ADC values of the two types of benign lesions and chondrosarcomas were not significantly different. However, the mean ADC value of solitary bone cysts (mean ϮSD, 2.57 Ϯ 0.13 ϫ 10 -3 mm 2 /second) was significantly higher than that of fibrous dysplasias and chondrosarcomas (2.0 Ϯ 0.21 ϫ 10 -3 mm 2 /second and 2.29 Ϯ 0.14 ϫ 10 -3 mm 2 /second, respectively, P Ͻ 0.05). None of the lesions with ADC values lower than 2.0 ϫ 10 -3 mm 2 /second were chondrosarcomas. Conclusion:Although there was some overlapping in the ADC values of chondrosarcomas, solitary bone cyst, and fibrous dysplasia, quantitative DWI may aid in the differential diagnosis of poorly contrast-enhanced and T2-prolonged bone masses.

PurposeTo evaluate the potential of diffusion‐weighted imaging (DWI) in distinguishing chronic expanding hematomas (CEHs) from malignant soft tissue tumors.Materials and MethodsWe performed conventional MRI and DWI of six CEHs and 31 malignant soft tissue tumors from 37 patients seen between May 2000 and November 2006. DWI was obtained with a single‐shot echo‐planar imaging (EPI) sequence using a 1.5T MR imager. The mean apparent diffusion coefficient (ADC) value was also calculated. We evaluated MRI findings of CEHs and compared ADC value of CEHs with malignant soft tissue tumors.ResultsOn conventional MRI, two of six CEHs were difficult to differentiate from malignant soft tissue tumors based on imaging findings. The mean ADC value of CEHs and malignant soft tissue tumors was 1.55 ± 0.121 × 10−3 mm2/sec and 0.92 ± 0.139 × 10−3 mm2/sec (mean ± SD), respectively. The mean ADC value of CEHs was significantly higher than that of malignant soft tissue tumors (P < 0.01). There was no overlap in the minimum ADC values among CEHs and malignant soft tissue tumors.ConclusionDWI is useful for differentiating between CEHs and malignant soft tissue tumors. J. Magn. Reson. Imaging 2008;28:1195–1200. © 2008 Wiley‐Liss, Inc.

Purpose: To evaluate the usefulness of diffusion-weighted imaging (DWI) for differentiating between desmoid tumors and malignant soft tissue tumors. Materials and Methods:Conventional MRI and DWI were performed for 8 desmoid tumors and 74 malignant soft tissue tumors. DWI was obtained with a single-shot echoplanar imaging sequence using a 1.5 Tesla (T) MR imager. DW images were acquired with motion-probing gradient pulses applied along three directions (x, y, and z axes) with three b-factors (0, 500, and 1000 s/mm 2 ). Two observers blinded to clinical information measured three regions of interest within the solid tumor and selected a minimum apparent diffusion coefficient ( ) in each lesion. The mean ADC of desmoid tumors was calculated and compared with that of malignant soft tissue tumors using the Mann-Whitney U test. Results:The mean ADC of desmoid tumors and malignant soft tissue tumors was 1.36 6 0.48 Â 10 À3 mm 2 /s and 0.88 6 0.20 Â 10 À3 mm 2 /s (mean 6 SD), respectively. The mean ADC of the desmoid tumors was significantly higher than that of malignant soft tissue tumors (P < 0.01).Conclusion: DWI is considered to be useful for differentiating between desmoid tumors and malignant soft tissue tumors. In the future, further investigation in a large series is necessary.

Purpose: To detect differences in magnetic resonance imaging (MRI) between chondroblastic osteosarcoma and the other types of osteosarcomas or chondrosarcomas using gadolinium-enhanced versus diffusion-weighted sequences. Materials and Methods:Contrast-enhanced MRI and diffusion-weighted imaging (DWI) were performed in five chondroblastic osteosarcoma (CO) cases, 17 other types of osteosarcomas (OS), and 18 chondrosarcomas (CS). DWI was obtained with a single-shot echo-planar imaging (EPI) sequence using a 1.5T MR imager. The apparent diffusion coefficients (ADCs) of the minimum and maximum values were also obtained. The contrast-enhancement pattern was evaluated and minimum-maximum ADC value of CO was compared with other types of OS and CS.Results: Both CO and CS showed a similar enhancement pattern; both showed septonodular and peripheral rim enhancement. The minimum ADC value of CO (1.24 Ϯ 0.10 ϫ 10 Ϫ3 mm 2 /sec) was significantly higher than that of other types of OS (0.84 Ϯ 0.15 ϫ 10 Ϫ3 mm 2 /sec) and was significantly lower than that of CS (1.64 Ϯ 0.20 ϫ 10 Ϫ3 mm 2 /sec). In addition, the maximum ADC value of CO (2.28 Ϯ 0.20 ϫ 10 Ϫ3 mm 2 /sec) was significantly higher than that of other types of OS (1.33 Ϯ 0.26 ϫ 10 Ϫ3 mm 2 /sec).Conclusion: DWI appears to be more useful for differentiating between chondroblastic osteosarcoma and chondrosarcoma or other types of osteosarcoma than Gd-enhanced MRI.

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