Semaphorin 4C Promotes Macrophage Recruitment and Angiogenesis in Breast Cancer.

Semaphorins are a large family of evolutionarily conserved morphogenetic molecules that are associated with repelling axonal guidance. Intriguingly, recent researches indicate that semaphorins are involved in cancer progression. Semaphorin 4C (SEMA4C) has long been considered a neuronal migration gene, but we detected that it is also highly expressed in many malignant human cancers. During an investigation of subcutaneous tumor models, we found that SEMA4C expression promoted tumor growth and progression. We discovered that SEMA4C was involved in maintaining tumor cell self-renewal, likely by regulating the p53 pathway. Inhibiting the expression of endogenous SEMA4C in tumor cells impaired growth and induced senescence and cell-cycle arrest in the G2-phase. In addition, we found that SEMA4C induced the production of angiogenin and colony-stimulating factor-1 (CSF-1) in tumor cells by activating the NF-κB pathway in a plexinB2-dependent manner. In conclusion, SEMA4C expression in breast cancer cells promotes cancer cell proliferation, macrophage recruitment, and angiogenesis. Thus, inhibition of SEMA4C activity may be a novel therapeutic strategy for human breast cancer. IMPLICATIONS: In breast cancer, therapeutic targeting of the SEMA4C pathway may prevent tumor growth, angiogenesis, metastasis, and progression.

Breast diseases: color Doppler US in differential diagnosis.

PURPOSE: To subjectively and semiquantitatively evaluate color Doppler signals on images of breast lesions. MATERIALS AND METHODS: A 5-MHz ultrasound (US) system was used to examine 210 new breast lesions. Signals were evaluated subjectively with an analog scale. A semiquantitative scoring system involved analysis of the average number of vessels per square centimeter and average density of color pixels. RESULTS: Vessels were detected in 57 of 58 cancers (mean, 0.11 vessels per square centimeter, occupying 1.76% of the scan area). Color Doppler scores had no correlation with conventional prognostic indicators such as lymph node status or survival. Fewer vessels per square centimeter (mean, 0.06) occupying a smaller area (mean, 0.41%) were detected in the five fibroadenomas (n = 36) that showed color Doppler signals. Most cases (99 of 104 [96%]) of benign breast changes had no color Doppler signals. CONCLUSION: Color Doppler signals in a lesion otherwise thought to be benign should prompt a biopsy, while the absence of signals in an indeterminate lesion is reassuring.

[Doppler ultrasound differentiation of benign and malignant breast tumors]. / Die dopplersonographische Differenzierung von benignen und malignen Mammatumoren.

Before surgery we studied the blood flow in and around 59 breast tumours (35 malignant and 24 benign) and investigated a correlation with the histology. The most decisive factors were the maximum end-diastolic frequency B (probability greater than magnitude of z = 0.0009) and the mean frequency F mean (probability greater than magnitude of z = 0.0017). The maximum systolic frequency A, the resistance index Ri, the diastolic angle W and the pulsatility index Pi showed less significant differences between malignant and benign histological types. In a retrospective survey, we tried to confirm the definitive histology by our Doppler results. In this, we failed in 17.14%--of malignant cases and in 33.33% in the cases of benign tumours.

Continuous-wave and pulsed Doppler studies of the breast: clinical results and effect of transducer frequency.

Malignant growth requires a high metabolism. This allows the differentiation of lesions by Doppler measurements of their vascularisation. In this study of 224 patients with 45 malignancies (37 breast cancers and 8 local recurrences), 87% of the cases were correctly identified. Differentiation of palpable lesions was possible in 93%. The flow in normal breast arteries was studied as well as in carcinomas, comparing continuous-wave (CW) Doppler with frequencies at 4 and 8 MHz. To improve flow evaluations in nonpalpable lesions, pulsed Doppler was used at 3 MHz and color mapping systems at 5 MHz in another 37 patients. Color Doppler at 5 MHz identified 17 of the 21 malignancies; in all cases pulsed Doppler at 3 MHz failed.

Evaluation of flow in nodular tumors of the breast by Doppler and duplex scanning.

Evaluation of flow in nodular tumors of the breast may be performed by Doppler and computerized frequency analysis. In 46 nodules of the breast (22 malignant) the nodular flow velocity and frequency analysis revealed a faster flow with a significantly higher peak frequency and mean velocity. The intensity of sound which may be considered an index of the entity of flow in the nodule was larger than that observed in the normal surrounding breast tissue. In malignant nodules and generally in fast growing nodules the flow velocity and intensity was even larger. The flow intensity and velocity was also well correlated with the growth rate as reported by single patients. In elder patients a slow rate of growth even in tumors of larger size was associated with a significantly increased flow in comparison with the normal breast tissue but this increase was not particularly large when compared with fast growing nodules in younger subjects. In conclusion the evaluation of flow characteristics (mainly velocity, frequency analysis and intensity) may be a useful index of the growth rate of nodular tumors of the breast and these data may be useful to evaluate and monitor the evolution and pathophysiology of these nodules.

Blood flow and reactivity to noradrenaline in induced and autotransplanted DMBA rat mammary neoplasia.

Blood flow during the 'resting condition' and during noradrenaline infusion was compared by means of a microsphere tracer technique in induced DMBA-tumours along the mammary ridge and in autotransplanted tumours, as well as in abdominal skin, skeletal muscle, liver and kidneys. During 'resting conditions' the blood flow of tumours transplanted into skeletal muscle of the hindlimb, liver and kidney was similar to that of the non-transplanted tumours present along the mammary ridges. A pronounced decrease of blood flow upon moderate noradrenaline infusion was characteristic of autotransplanted as well as non-transplanted tumours, which contrasted to the insignificant reaction of skeletal muscle. The striking similarities in blood flow and reactivity of non-transplanted DMBA tumours and autotransplanted ones, and the dissimilarities of the transplanted tumours and the hosting tissues, favour the idea that these tumours regulate their blood supply irrespective of host tissue.

Tumour detection by ultrasonic Doppler blood-flow signals.

Ultrasonic Doppler blood-flow signals which seem to be associated with malignant tumour neovascularization have been detected in the female breast. No such signals have been detected from cysts. This discovery may lead to the development of a highspeed ultrasonic Doppler scanner which might make breast screening for cancer practicable.