Expression of Diverse Angiogenesis Factor in Different Stages of the 4T1 Tumor as a Mouse Model of Triple-Negative Breast Cancer

Abstract

Purpose: Triple-negative breast cancer (TNBC) is specified by high vascularity and repetitious metastasis. Although several studies have indicated that angiogenesis has an important role in invasive breast cancer, a suitable model of TNBC that can show the exact onset of angiogenesis factors still needs to be developed. The purpose of this study is to determine the expression level of angiogenesis factors in different clinical stages of the 4T1 tumor as TNBC mouse model. Methods: Twenty mice were injected by the 4T1 cell line, and four mice selected as healthy controls. Following by tumor induction, the mice were randomly put into four groups, each contains four mice. Once the tumor volume reached to the early stage (<100 mm3 ), intermediate stage (100-300 mm3 ), advanced stage (300-500 mm3 ), and end stage (>500 mm3 ), they were removed by surgery. Then, the expression levels of Hif1α, VEGFR1, and VEGFR2 genes, as well as tumor markers of VEGF, bFGF and CD31, were evaluated by qPCR and immunohistochemistry (IHC) respectively. The statistical analysis was done by SPSS version 16. Results: TNBC tumors were confirmed and multi-foci metastasis in the lung were seen. The mRNA and protein expression levels of the angiogenesis factors increased in the early stage and as the tumor grew, their expression level enhanced dramatically. Conclusion: The 4T1 syngeneic mouse tumor may serve as an appropriate TNBC model for further investigation of the angiogenesis and therapies. Moreover, angiogenesis factors are induced before the advanced stage, and anti-angiogenesis therapy is necessary to be considered at the first line of treatment in TBNC.

Desensitization of Capsaicin-Sensitive Afferents Accelerates Early Tumor Growth via Increased Vascular Leakage in a Murine Model of Triple Negative Breast Cancer

“…Considering the observed in vivo differences in intratumoral vascular leakage, CD3, CD31, and CD45 were selected as markers to further assess endothelial changes and immune-cell response (36)(37)(38). Semi-automated quantification of CD31 immunohistology within the annotated area of the tumor tissue harvested at the end of the experiment was not significantly different in RTX-pretreated and non-pretreated control animals (1.449 vs 1.599 relative mask area (rMA) (%); Figures 6A, B, D).…”

Acute toxicity and antitumor potential of 1,3,4‐trisubstituted‐1,2,3‐triazole dhmtAc‐loaded liposomes on a triple‐negative breast cancer model

“…TNBC is an invasive breast cancer due to its high vascularity and frequent metastatic rate to different organs, such as the lung and brain. [1,2] TNBC poor prognosis and the lower survival rate compared to other subtypes are attributed to the absence of estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2, which leads to repetitive metastasis and less than a 5-year survival rate of all cases. [3,4] Adjuvant systemic therapy is a typical treatment of TNBC patients by the combination of surgery, radiotherapy, and chemotherapy.…”

Ultrasensitive Detection of Ribonucleic Acid Biomarkers Using Portable Sensing Platforms Based on Organic Electrochemical Transistors

“…The 4T1 tumor model is developed by injecting 4T1 cancer cells into BALB/c mouse . The 4T1 tumor has the advantages of an easy transplant procedure, and its progressive behavior is very similar to human mammary cancer . The upregulation of miR-21 in blood is closely associated with 4T1 tumor progression, so it is assumed that miR-21 circulating in blood could show an increasing concentration with the growth of tumor.…”