The association between expressions of Ras and CD68 in the angiogenesis of breast cancers

Abstract

ObjectiveAngiogenesis is a critical step of breast cancer metastasis. Oncogenic Ras promotes the remodeling of cancer microenviroment. Tumor-associated macrophages (TAMs) are a prominent inflammatory cell population emerging in the microenviroment and facilitating the angiogenesis and metastasis. In the present study, we tried to investigate the relationship between the expression of Ras and infiltration of TAM, both of which could further promote angiogenesis.MethodsExpressions of Ras, CD68 and CD34 were assessed by immunohistochemistry. The infiltration of macrophages was evaluated by counting the number of CD68+ cells. Vessel endothelial cells were defined as CD34+ cells. Angiogenesis vascularity was defined by microvessel density (MVD) assay through counting the number of vessels per field counted in the area of highest vascular density. The Kaplan–Meier survival analysis was used to estimate the overall survival (OS). Macrophages were derived from monocytes in the presence of macrophage colony-stimulating-factor (MCSF). Breast cancer cells were treated with macrophage-conditioned medium (MCM) and tested the expressions of K-, H- and N-Ras by using realtime-PCR.ResultsRas positive status was correlated with ER, PR and Her-2 positivity, larger tumour size and lymph node metastasis, as well as higher TNM stages. A higher number of CD68+ cells was correlated with larger tumour size, higher TNM stages and Her-2 positivity. Both Ras positivity and infiltration of CD68+ macrophages correlated with poor OS. The number of CD68+ cells was positively correlated with the expression of Ras. Treatment with MCM did not up-regulate but repressed the expression of Ras. Both up-regulation of Ras and infiltration of TAMs correlated with increased MVD.ConclusionExpression of Ras and infiltration of TAM were positively correlated, and both participated in angiogenesis. Elevated Ras could be responsible for the infiltration of TAM.

FH535, a β-catenin pathway inhibitor, represses pancreatic cancer xenograft growth and angiogenesis

“…Ki-67 immunoreactivity was expressed as the mean percentage of tumor cells with the highest nuclear labeling after manual counting of 20 hotspot areas. Endothelial cells were marked with anti-CD34 antibody and subjected to MVD and angiogenesis vascularity evaluation [70] (Supplementary Methods).…”

Scavenger Receptors

“…The high density of CD68 + TAMs is accompanied with high stromal and serum levels of VEGF. There is an association between expressions of CD68 and Ras in the angiogenesis of breast cancer (Li et al, 2015). Upregulation of VEGF in macrophages by IR is believed to decrease the antitumor efficacy of radiotherapy (Meng et al, 2010), suggesting that the CD68 + TAMs may also be an indicator for the outcome of cancer treatment, such as radiotherapy.…”

Inflammatory stimuli promote growth and invasion of pancreatic cancer cells through NF-κB pathway dependent repression of PP2Ac

“…13,54 Buffy coats containing mononuclear cells were collected from the blood of healthy individual donors at the First Affiliated Hospital of Soochow University with an approved Institutional Review Board application (the Committee on Medical Ethics, the First Affiliated Hospital of Soochow University). Primary blood monocytes were isolated by density-gradient centrifugation through Ficol/Hypaque (Amersham Bioscience, Piscataway, NJ), suspended (8£10 6 cells/ml) in DMEM medium (Gibco) with 10% heat-inactivated human serum (Sigma, St. Louis, MO), and seeded in culture dishes.…”