2. Academic Validation
  3. A subpopulation of luminal progenitors secretes pleiotrophin to promote angiogenesis and metastasis in inflammatory breast cancer

A subpopulation of luminal progenitors secretes pleiotrophin to promote angiogenesis and metastasis in inflammatory breast cancer

  • Cancer Res. 2024 Mar 20. doi: 10.1158/0008-5472.CAN-23-2640.
Mengmeng Zhang 1,  Kaiwen Zhou 2,  Zilin Wang 2,  Ting Liu 3,  Laura E Stevens 4,  Filipa Lynce 5,  Wendy Y Chen 4,  Sui Peng 1,  Yubin Xie 6,  Duanyang Zhai 2,  Qianjun Chen 7,  Yawei Shi 8,  Huijuan Shi 9,  Zhongyu Yuan 3,  Xiaoping Li 10,  Juan Xu 11,  Zhenhai Cai 12,  Jianping Guo 13,  Nan Shao 8,  Ying Lin 8
Affiliations

Affiliations

  • 1 First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
  • 2 First Affiliated Hospital of Sun Yat-sen University, China.
  • 3 Sun Yat-sen University Cancer Center, Guangzhou, China.
  • 4 Dana-Farber Cancer Institute, Boston, MA, United States.
  • 5 Dana-Farber/Harvard Cancer Center, Boston, MA, United States.
  • 6 Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 7 Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, China.
  • 8 First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, P.R.China., Guangdong, China., China.
  • 9 First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
  • 10 Jiangmen Central Hospital, China.
  • 11 Guangdong Province Women and Children Hospital, China.
  • 12 Jieyang People's Hospital, Jieyang, China.
  • 13 First Affiliated Hospital of Sun Yat-sen University, guangzhou, guangdong, China.
PMID: 38507720 DOI: 10.1158/0008-5472.CAN-23-2640
Abstract

Inflammatory breast Cancer (IBC) is a highly aggressive subtype of breast Cancer characterized by rapidly arising diffuse erythema and edema. Genomic studies have not identified consistent alterations and mechanisms that differentiate IBC from non-IBC tumors, suggesting that the microenvironment could be a potential driver of IBC phenotypes. Here, using single-cell RNA Sequencing, multiplex staining, and serum analysis in IBC patients, we identified enrichment of a subgroup of luminal progenitor (LP) cells containing high expression of the neurotropic cytokine pleiotrophin (PTN) in IBC tumors. PTN secreted by the LP cells promoted angiogenesis by directly interacting with the NRP1 receptor on endothelial tip cells located in both IBC tumors and the affected skin. NRP1 activation in tip cells led to recruitment of immature perivascular cells in the affected skin of IBC, which are correlated with increased angiogenesis and IBC metastasis. Together, these findings reveal a role for crosstalk between LPs, endothelial tip cells, and immature perivascular cells via PTN-NRP1 axis in the pathogenesis of IBC, which could lead to improved strategies for treating IBC.

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