Preventing tumor progression to the bone by induced tumor-suppressing MSCs

Xun Sun1,2, Kexin Li1,2, Rongrong Zha1,2

  • 1Department of Pharmacology, College of Pharmacy, Harbin Medical University, Harbin 150081, China.

Theranostics
|April 16, 2021
PubMed

Insights

Induced tumor-suppressing mesenchymal stem cells (iTS MSCs) show promise in preventing breast cancer bone metastasis. These modified MSCs reduced tumors and protected bone by downregulating tumor-promoting genes and inhibiting osteoclast development.

Area of Science:

  • Oncology
  • Stem Cell Biology
  • Cancer Metastasis

Background:

  • Advanced breast cancer frequently metastasizes to bone, with limited effective treatment options.
  • Mesenchymal stem cells (MSCs) are being investigated for their therapeutic potential in cancer.
  • Modifying MSCs may enhance their anti-cancer properties.

Purpose of the Study:

  • To investigate the potential of induced tumor-suppressing (iTS) mesenchymal stem cells (MSCs) to prevent bone metastasis in breast cancer.
  • To determine if overexpressing specific genes in MSCs can confer tumor-suppressing capabilities.
  • To evaluate the therapeutic efficacy of iTS MSCs in preclinical models.

Main Methods:

  • Generated iTS MSCs by overexpressing Lrp5, β-catenin, Snail, or Akt.
  • Utilized a mouse model of mammary tumors and bone metastasis.
  • Analyzed human breast cancer tissues, cell lines, and MSC-derived conditioned medium (MSC CM) using proteomics.

Main Results:

  • MSC CM from iTS MSCs reduced mammary tumors and suppressed tumor-induced osteolysis in a mouse model.
  • Downregulation of tumor-promoting genes (e.g., CXCL2, LIF) and PDL1 observed.
  • Enrichment of heat shock protein 90 (Hsp90ab1), calreticulin (Calr), and peptidylprolyl isomerase B (Ppib) in MSC CM as atypical tumor suppressors.
  • Selective inhibition of tumor cells over non-tumor cells by specific iTS MSC CMs and proteins.
  • Suppression of bone-resorbing osteoclast development by MSC CMs.

Conclusions:

  • iTS MSCs demonstrate significant anti-tumor effects, protecting bone from breast cancer metastasis.
  • Overexpression of selected genes can transform MSCs into potent tumor suppressors.
  • These findings suggest novel therapeutic strategies targeting bone metastasis in advanced breast cancer.

Related Concept Videos

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...
5.2K
Stem Cell Therapy for Tissue Regeneration01:21

Stem Cell Therapy for Tissue Regeneration

Stem cell therapy is a method used in regenerative medicine to repair and restore function to damaged tissues and organs. Stem cells have the potential to proliferate and differentiate into various tissue types, making them ideal candidates for tissue regeneration. For example, hematopoietic stem cell transplants are commonly used in blood cancer treatment to replenish damaged bone marrow and restore healthy blood cells.
Types of Stem Cells used in Stem Cell Therapy
The two main cell...
4.3K
Cancer Stem Cells and Tumor Maintenance02:40

Cancer Stem Cells and Tumor Maintenance

Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.2K