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Studies conducted on mice have undoubtedly shown that chemotherapy drugs caused changes in non-cancer cells that made this process possible
Three hours after the injection, the cancer cells penetrated the fragile junctions between the blood vessels in the lungs, and combined with the underlying structures of these blood vessels to avoid being washed away by the bloodstream
Tsonwin Hai, professor of biochemistry and pharmacology at Ohio State University and senior author of the study, said: "This is a crucial step for cancer cells to enter the second position
"This is a warning to the use of chemotherapy
The research was recently published in the online edition of the International Journal of Molecular Sciences
Hai has been studying the basis of cancer metastasis for many years.
The new study focuses on the effect of the chemotherapy drug cyclophosphamide on non-cancer cells before the cancer appears, with the focus on the lung as the site of metastasis
The researchers injected a dose of chemotherapeutics into mice and waited 4 days for the mice to metabolize and excrete the drug
Once in the lungs, if the animal is given chemotherapy in advance, cancer cells are more likely to adhere to the blood vessel walls
"The endothelial cells on the lining of blood vessels are like a brick wall, each brick wall is tightly glued together," said Hai, who is also a researcher at the Ohio State University Comprehensive Cancer Center
"We also found that chemotherapy changes the underlying basement membrane, so once the cancer cells squeeze through, they will find a place to grab it
Hai said that in mice in the control group that did not receive chemotherapy, the adhesion of cancer cells to the blood vessel wall was relatively low
The research team determined that the presence of cyclophosphamide caused an increase in the level of an enzyme called MMP-2 in the blood.
For decades, scientists have focused on studying the effects of chemotherapy on the intrinsic properties of cancer cells that allow cancer cells to survive, resist chemotherapy and spread
"We are here to focus on how chemotherapy affects non-cancerous lung cells - the second site is in our model, not in the primary tumor, because the escape of cancer cells from the primary tumor is not a late event - it can happen very early.
"The effect of chemotherapy on non-cancer cells actually changes these cells, and these changes help the development of cancer cells
This work was partially supported by the U.
S.
Department of Defense
.
The co-authors are Justin Middleton and Subhakeertana Sivakumar from Ohio
.
Journal Reference :
Justin D.
Middleton, Subhakeertana Sivakumar, Tsonwin Hai.
Chemotherapy-Induced Changes in the Lung Microenvironment: The Role of MMP-2 in Facilitating Intravascular Arrest of Breast Cancer Cells .
International Journal of Molecular Sciences , 2021; 22 (19): 10280 DOI : 10.
3390/ijms221910280