Crosstalk between tumor cells and lymphocytes modulates heparanase expression

Area of Science:

• Biochemistry
• Cell Biology
• Cancer Research

Background:

• Heparanase (HPSE) degrades heparan sulfate (HS), promoting tumor growth and metastasis.
• Heparanase-2 (HPSE2) is a non-catalytic homolog of HPSE.
• Increased HPSE and HPSE2 expression is observed in lymphocytes of breast cancer patients.

Purpose of the Study:

• To investigate the mechanisms behind the upregulation of heparanases (HPSE and HPSE2) in circulating lymphocytes.
• To understand the role of tumor cells and heparan sulfate in this upregulation.

Main Methods:

• Co-culture of lymphocytes from healthy women with MCF-7 breast cancer cells.
• Evaluation of heparanase protein levels via immunocytochemistry.
• Quantification of heparanase mRNA expression using RT-PCR.

Main Results:

• Co-culture medium stimulated HPSE and HPSE2 expression in lymphocytes.
• Treatment with anti-HS antibody or heparitinase II inhibited this upregulation.
• Exogenous HS addition enhanced heparanase expression; exosomes from co-cultured and MCF-7 cells showed higher HS levels.

Conclusions:

• Heparan sulfate (HS) mediates the expression of heparanases in circulating lymphocytes.
• Tumor cell-secreted HS, potentially via exosomes, plays a key role in upregulating heparanases.
• This suggests a crosstalk mechanism between tumor cells and lymphocytes involving secreted HS.