Related Experiment Video

Updated: Jun 7, 2025

Osteoclast Derivation from Mouse Bone Marrow
06:17

Osteoclast Derivation from Mouse Bone Marrow

Published on: November 6, 2014

24.1K

Osteoblast-Derived ECM1 Promotes Anti-Androgen Resistance in Bone Metastatic Prostate Cancer

Xinwen Wang1,2, Min Wang2,3, Qijun Lin1,2

  • 1Department of Orthopedic Surgery, the First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, 510080, China.

Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
|November 20, 2024
PubMed

Insights

Osteoblasts secrete extracellular matrix protein 1 (ECM1) that drives enzalutamide (ENZ) resistance in bone metastatic prostate cancer by activating the MAPK pathway. Inhibiting ECM1 or enolase 1 (ENO1) restores sensitivity to ENZ.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Acquired resistance to enzalutamide (ENZ) is a major challenge in advanced bone metastatic prostate cancer.
  • The bone microenvironment plays a critical role in prostate cancer progression and treatment resistance.

Purpose of the Study:

  • To elucidate the mechanism by which osteoblasts contribute to anti-androgen resistance in prostate cancer.
  • To identify novel therapeutic targets for overcoming enzalutamide resistance.

Main Methods:

  • In vitro and in vivo models of bone metastatic prostate cancer.
  • Analysis of extracellular matrix protein 1 (ECM1) and enolase 1 (ENO1) expression and function.
  • Western blotting to assess protein phosphorylation and signaling pathway activation (MAPK).
  • Pharmacological inhibition of ECM1 and ENO1.

Main Results:

  • Enzalutamide treatment increases osteoblast-derived ECM1 secretion in the bone microenvironment.
  • ECM1 binds to enolase 1 (ENO1) on prostate cancer cells, promoting Y189 phosphorylation and activating the MAPK pathway.
  • This ECM1-ENO1-MAPK axis drives tumor cell proliferation and enzalutamide resistance.
  • Inhibition of ECM1 or ENO1 (using phosphonoacetohydroxamate, PhAH) restores prostate cancer cell sensitivity to enzalutamide.

Conclusions:

  • Osteoblast-derived ECM1 promotes enzalutamide resistance in bone metastatic prostate cancer via the ENO1-MAPK signaling pathway.
  • ECM1 and ENO1 represent potential therapeutic targets for overcoming treatment resistance in castration-resistant prostate cancer.
Keywords:
ECM1ENO1enzalutamide resistanceosteoblastprostate cancer

More Related Videos

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma08:07

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma

Published on: April 12, 2019

7.2K
Intra-Cardiac Injection of Human Prostate Cancer Cells to Create a Bone Metastasis Xenograft Mouse Model06:32

Intra-Cardiac Injection of Human Prostate Cancer Cells to Create a Bone Metastasis Xenograft Mouse Model

Published on: November 4, 2022

4.5K

Related Concept Videos

The Tumor Microenvironment02:17

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...
6.5K
The Extracellular Matrix01:29

The Extracellular Matrix

Overview
In order to maintain tissue organization, many animal cells are surrounded by structural molecules that make up the extracellular matrix (ECM). Together, the molecules in the ECM maintain the structural integrity of tissue as well as the remarkable specific properties of certain tissues.
Composition of the Extracellular Matrix
The extracellular matrix (ECM) is commonly composed of ground substance, a gel-like fluid, fibrous components, and many structurally and functionally diverse...
8.8K
Mesenchymal Stem Cells01:19

Mesenchymal Stem Cells

Mesenchymal stem cells (MSCs) are adult stem cells that can differentiate into most connective tissue cell types, except for hematopoietic cells, depending upon the source of MSCs. For example, bone-marrow-derived MSCs (BM-MSCs) can differentiate into osteocytes, hepatocytes, and pancreatic and neuronal cells. MSCs can be isolated from various sources such as bone marrow, placenta, adipose tissue, teeth, and Wharton’s jelly, a gelatinous substance in the umbilical cord. The ease of their...
4.6K
Role of Matrix Metalloproteases in Degradation of ECM01:23

Role of Matrix Metalloproteases in Degradation of ECM

Matrix metalloproteases (MMPs) are enzymes involved in the hydrolysis of proteins and glycoproteins of the extracellular matrix. MMPs are essential for the migration and proliferation of cells through the dense matrix network, throughout embryonic development, and throughout morphogenesis. The first MMP activity discovered was a collagenase in a tadpole's tail undergoing metamorphosis. The active collagen deposition and modifications lead to the morphogenesis of tadpoles into the adult...
2.3K
Osteoclasts in Bone Remodeling01:31

Osteoclasts in Bone Remodeling

Osteoclasts are cells responsible for bone resorption and remodeling. They originate from hematopoietic progenitor cells present in the bone marrow. Numerous progenitor cells fuse to form multinucleated cells, each with 10-20 nuclei. A single osteoclast has a diameter of 150 to 200 µM. These cells have ruffled borders that break down the underlying bone tissue and release minerals such as calcium into the blood in bone resorption. Osteoclasts cling to bones with their ruffled edges during...
2.8K