Gonzalez-Pons Romina, Bernard Jamie J
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI, United States.
Department of Medicine, Michigan State University, East Lansing, MI, United States.
Front Oncol. 2024 Sep 5;14:1394039. doi: 10.3389/fonc.2024.1394039. eCollection 2024.
Tumor metastasis is the main cause of death in triple-negative breast cancer (TNBC) patients. TNBC is the most aggressive subtype of breast cancer lacking the expression of estrogen, progesterone, and human epidermal growth factor 2 receptors, thereby rendering it insensitive to targeted therapies. It has been well-established that excess adiposity contributes to the progression of TNBC; however, due to the aggressive nature of this breast cancer subtype, it is imperative to determine how multiple factors can contribute to progression. Therefore, we aimed to investigate if exposure to an environmental carcinogen could impact a pre-existing obesity-promoted cancer. We utilized a spontaneous lung metastatic mouse model where 4T1 breast tumor cells are injected into the mammary gland of BALB/c mice. Feeding a high fat diet (HFD) in this model has been shown to promote tumor growth and metastasis. Herein, we tested the effects of both a HFD and benzo(a)pyrene (B[a]P) exposure. Our results indicate that diet and B[a]P had no tumor promotional interaction. However, unexpectedly, our findings reveal an inhibitory effect of B[a]P on body weight, adipose tissue deposition, and tumor volume at time of sacrifice specifically under HFD conditions.
肿瘤转移是三阴性乳腺癌(TNBC)患者死亡的主要原因。TNBC是乳腺癌中最具侵袭性的亚型,缺乏雌激素、孕激素和人表皮生长因子2受体的表达,因此对靶向治疗不敏感。众所周知,肥胖会促进TNBC的进展;然而,由于这种乳腺癌亚型的侵袭性,确定多种因素如何促进其进展至关重要。因此,我们旨在研究暴露于环境致癌物是否会影响已存在的肥胖促进型癌症。我们使用了一种自发肺转移小鼠模型,将4T1乳腺肿瘤细胞注射到BALB/c小鼠的乳腺中。在该模型中喂食高脂肪饮食(HFD)已被证明可促进肿瘤生长和转移。在此,我们测试了HFD和苯并[a]芘(B[a]P)暴露的影响。我们的结果表明,饮食和B[a]P没有肿瘤促进相互作用。然而,出乎意料的是,我们的研究结果揭示了在HFD条件下,B[a]P对体重、脂肪组织沉积以及处死时的肿瘤体积具有抑制作用。