lancet-header

Preprints with The Lancet is part of SSRN´s First Look, a place where journals identify content of interest prior to publication. Authors have opted in at submission to The Lancet family of journals to post their preprints on Preprints with The Lancet. The usual SSRN checks and a Lancet-specific check for appropriateness and transparency have been applied. Preprints available here are not Lancet publications or necessarily under review with a Lancet journal. These preprints are early stage research papers that have not been peer-reviewed. The findings should not be used for clinical or public health decision making and should not be presented to a lay audience without highlighting that they are preliminary and have not been peer-reviewed. For more information on this collaboration, see the comments published in The Lancet about the trial period, and our decision to make this a permanent offering, or visit The Lancet´s FAQ page, and for any feedback please contact preprints@lancet.com.

Palmitic Acid-Activated GPRS/KLF7/CCL2 Pathway Contributes to the Crosstalk between Bone Marrow Adipocytes and Prostate Cancer

31 Pages Posted: 18 Oct 2021

See all articles by Jingzhou Wang

Jingzhou Wang

Shihezi University - Medical College

Cuizhe Wang

Shihezi University - Medical College

Bingqi Yang

Shihezi University - Medical College

Huai Pang

Shihezi University - Medical College

Keru Chen

Shihezi University - Medical College

Jiale Feng

Shihezi University - Medical College

Yuchun Deng

Shihezi University - Medical College

Xueting Zhang

Shihezi University - Medical College

Chenggang Yuan

Shihezi University - Medical College

Wei Li

Shihezi University - Medical College

Jianxin Xie

Shihezi University - Medical College

Jun Zhang

Shihezi University - Medical College

More...

Abstract

Obesity-induced abnormal bone marrow microenvironment is an important risk factor for bone metastasis of prostate cancer (PCa). This study was intended to investigate whether obesity-induced elevated palmitic acid (PA), the most abundant free fatty acids (FFAs), increased CCL2 through GPRs/KLF7 pathway in bone marrow adipocytes(BMA) to promote the growth and metastasis of PCa. In BALB/c nude mice, we found that the distribution of BMA in the bone marrow cavity of high fatty diet(HFD) mice were significantly higher than normal diet(ND) mice. More importantly, HFD-induced obesity promotes the KLF7/CCL2 expression of BMA and PCa cells growth in bone marrow cavity. In vitro, conditioned medium with elevated CCL2 obtained from BMA incubated with PA (CM-BMA-PA) was used to deal with PCa cell lines, and a significant increase in the proliferation, invasion, and migration ability was found in PC3 cells. KLF7 could strikingly increase the CCL2 expression and release levels of BMA. Moreover, GPR40/120 involved in PA-induced high KLF7/CCL2 levels of BMA to promote malignant progression of PC3 cells. In conclusion, PA-activated GPRs/KLF7/CCL2 pathway of BMA promotes the growth and metastasis of prostate cancer.

Funding: This research was funded by the Natural Science Foundation of China (grant number 81760518), Xinjiang Production and Construction Corps Key Areas Innovation Team Project (grant number 2018CB002), the Scientific and Technological Research Project of Xinjiang Production and Construction Corps (grant number 2018AB018, 2021AB028), and Projects of Shihezi University (grant number ZZZC202017A, ZZZC201817A, GJHZ201703).

Declaration of Interest: None to declare.

Ethical Approval: All experiments involving mice were performed in accordance with the protocol approved by the Medical Ethics Committee at First Affiliated Hospital, Shihezi University School of Medicine (reference number: A2017-115-01).

Keywords: Palmitic acid, bone marrow adipocytes, GPRs/KLF7/CCL2, prostate cancer

Suggested Citation

Wang, Jingzhou and Wang, Cuizhe and Yang, Bingqi and Pang, Huai and Chen, Keru and Feng, Jiale and Deng, Yuchun and Zhang, Xueting and Yuan, Chenggang and Li, Wei and Xie, Jianxin and Zhang, Jun, Palmitic Acid-Activated GPRS/KLF7/CCL2 Pathway Contributes to the Crosstalk between Bone Marrow Adipocytes and Prostate Cancer. Available at SSRN: https://ssrn.com/abstract=3944542 or http://dx.doi.org/10.2139/ssrn.3944542

Jingzhou Wang

Shihezi University - Medical College ( email )

Xinjiang
China

Cuizhe Wang

Shihezi University - Medical College ( email )

Xinjiang
China

Bingqi Yang

Shihezi University - Medical College ( email )

Xinjiang
China

Huai Pang

Shihezi University - Medical College ( email )

Xinjiang
China

Keru Chen

Shihezi University - Medical College ( email )

Xinjiang
China

Jiale Feng

Shihezi University - Medical College ( email )

Xinjiang
China

Yuchun Deng

Shihezi University - Medical College ( email )

Xinjiang
China

Xueting Zhang

Shihezi University - Medical College ( email )

Xinjiang
China

Chenggang Yuan

Shihezi University - Medical College ( email )

Xinjiang
China

Wei Li

Shihezi University - Medical College ( email )

Xinjiang
China

Jianxin Xie

Shihezi University - Medical College ( email )

Xinjiang
China

Jun Zhang (Contact Author)

Shihezi University - Medical College ( email )

Xinjiang
China

Click here to go to TheLancet.com

Paper statistics

Downloads
38
Abstract Views
307
PlumX Metrics