Research output: Contribution to journal › Article › peer-review
Novel mechanism of drug resistance triggered by tumor-associated macrophages through Heat Shock Factor-1 activation. / Nikotina, Alina D. ; Vladimirova, Snezhana A. ; Kokoreva, Nadezhda E. ; Nevdakha, Valeria A. ; Lazarev, Vladimir F. Lazarev; Kuznetcova, Liubov S.; Komarova, Elena Y. ; Suezov, Roman V. ; Ефремов, Сергей Михайлович; Леонова, Елизавета Андреевна; Kartsev, Viktor G. ; Aksenov, Nikolay D. ; Margulis, Boris A.; Guzhova, Irina V. .
In: Cancer Immunology, Immunotherapy, Vol. 73, No. 2, 25, 27.01.2024.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Novel mechanism of drug resistance triggered by tumor-associated macrophages through Heat Shock Factor-1 activation
AU - Nikotina, Alina D.
AU - Vladimirova, Snezhana A.
AU - Kokoreva, Nadezhda E.
AU - Nevdakha, Valeria A.
AU - Lazarev, Vladimir F. Lazarev
AU - Kuznetcova, Liubov S.
AU - Komarova, Elena Y.
AU - Suezov, Roman V.
AU - Ефремов, Сергей Михайлович
AU - Леонова, Елизавета Андреевна
AU - Kartsev, Viktor G.
AU - Aksenov, Nikolay D.
AU - Margulis, Boris A.
AU - Guzhova, Irina V.
PY - 2024/1/27
Y1 - 2024/1/27
N2 - Macrophages constitute a major part of tumor microenvironment, and most of existing data demonstrate their ruling role in the development of anti-drug resistance of cancer cell. One of the most powerful protection system is based on heat shock proteins whose synthesis is triggered by activated Heat Shock Factor-1 (HSF1); the inhibition of the HSF1 with CL-43 sensitized A549 lung cancer cells to the anti-cancer effect of etoposide. Notably, analyzing A549 tumor xenografts in mice we observed nest-like pattern of co-localization of A549 cells demonstrating enhanced expression of HSF1 with macrophages, and decided to check whether the above arrangement has a functional value for both cell types. It was found that the incubation of A549 or DLD1 colon cancer cells with either human monocytes or THP1 monocyte-like cells activated HSF1 and increased resistance to etoposide. Importantly, the same effect was shown when primary cultures of colon tumors were incubated with THP1 cells or with human monocytes. To prove that HSF1 is implicated in enhanced resistance caused by monocytic cells, we generated an A549 cell subline devoid of HSF1 which did not respond to incubation with THP1 cells. The pharmacological inhibition of HSF1 with CL-43 also abolished the effect of THP1 cells on primary tumor cells, highlighting a new target of tumor-associated macrophages in a cell proteostasis mechanism.
AB - Macrophages constitute a major part of tumor microenvironment, and most of existing data demonstrate their ruling role in the development of anti-drug resistance of cancer cell. One of the most powerful protection system is based on heat shock proteins whose synthesis is triggered by activated Heat Shock Factor-1 (HSF1); the inhibition of the HSF1 with CL-43 sensitized A549 lung cancer cells to the anti-cancer effect of etoposide. Notably, analyzing A549 tumor xenografts in mice we observed nest-like pattern of co-localization of A549 cells demonstrating enhanced expression of HSF1 with macrophages, and decided to check whether the above arrangement has a functional value for both cell types. It was found that the incubation of A549 or DLD1 colon cancer cells with either human monocytes or THP1 monocyte-like cells activated HSF1 and increased resistance to etoposide. Importantly, the same effect was shown when primary cultures of colon tumors were incubated with THP1 cells or with human monocytes. To prove that HSF1 is implicated in enhanced resistance caused by monocytic cells, we generated an A549 cell subline devoid of HSF1 which did not respond to incubation with THP1 cells. The pharmacological inhibition of HSF1 with CL-43 also abolished the effect of THP1 cells on primary tumor cells, highlighting a new target of tumor-associated macrophages in a cell proteostasis mechanism.
KW - Animals
KW - Cell Line, Tumor
KW - DNA-Binding Proteins/metabolism
KW - Drug Resistance
KW - Etoposide/pharmacology
KW - Heat Shock Transcription Factors/metabolism
KW - Heat-Shock Response
KW - Humans
KW - Mice
KW - Transcription Factors/metabolism
KW - Tumor-Associated Macrophages/metabolism
UR - https://www.mendeley.com/catalogue/23ae940e-ffd9-3035-8968-a89e21d97138/
U2 - 10.1007/s00262-023-03612-2
DO - 10.1007/s00262-023-03612-2
M3 - Article
C2 - 38280079
VL - 73
JO - Cancer Immunology, Immunotherapy
JF - Cancer Immunology, Immunotherapy
SN - 0340-7004
IS - 2
M1 - 25
ER -
ID: 116335420