ADAM12 expression is upregulated in cancer cells upon radiation and constitutes a prognostic factor in rectal cancer patients following radiotherapy
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ADAM12 expression is upregulated in cancer cells upon radiation and constitutes a prognostic factor in rectal cancer patients following radiotherapy. / Piotrowski, Krzysztof Bartłomiej; Blasco, Laia Puig; Samsøe-Petersen, Jacob; Eefsen, Rikke Løvendahl; Illemann, Martin; Oria, Victor Oginga; Campos, Karla Iveth Aguilera; Lopresti, Alexia Mélanie; Albrechtsen, Reidar; Sørensen, Claus Storgaard; Sun, Xiao Feng; Kveiborg, Marie; Gnosa, Sebastian.
In: Cancer Gene Therapy, Vol. 30, 2023, p. 1369-1381.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - ADAM12 expression is upregulated in cancer cells upon radiation and constitutes a prognostic factor in rectal cancer patients following radiotherapy
AU - Piotrowski, Krzysztof Bartłomiej
AU - Blasco, Laia Puig
AU - Samsøe-Petersen, Jacob
AU - Eefsen, Rikke Løvendahl
AU - Illemann, Martin
AU - Oria, Victor Oginga
AU - Campos, Karla Iveth Aguilera
AU - Lopresti, Alexia Mélanie
AU - Albrechtsen, Reidar
AU - Sørensen, Claus Storgaard
AU - Sun, Xiao Feng
AU - Kveiborg, Marie
AU - Gnosa, Sebastian
N1 - Publisher Copyright: © 2023, The Author(s).
PY - 2023
Y1 - 2023
N2 - Radiotherapy is one of the most common cancer treatments, yet, some patients require high doses to respond. Therefore, the development of new strategies leans toward personalizing therapy to avoid unnecessary burden on cancer patients. This approach prevents the administration of ineffective treatments or uses combination strategies to increase the sensitivity of cancer cells. ADAM12 has been shown to be upregulated in many cancers and correlate with poor survival and chemoresistance, thus making it a potential candidate responsible for radioresistance. Here, we show that ADAM12 expression is upregulated in response to irradiation in both mouse and human cancer cells in vitro, as well as in tumor tissues from rectal cancer patients. Interestingly, the expression of ADAM12 following radiotherapy correlates with the initial disease stage and predicts the response of rectal cancer patients to the treatment. While we found no cell-autonomous effects of ADAM12 on the response of colon cancer cells to irradiation in vitro, depletion of ADAM12 expression markedly reduced the tumor growth of irradiated cancer cells when subcutaneously transplanted in syngeneic mice. Interestingly, loss of cancer cell-derived ADAM12 expression increased the number of CD31+FAP− cells in murine tumors. Moreover, conditioned medium from ADAM12−/− colon cancer cells led to increased tube formation when added to endothelial cell cultures. Thus, it is tempting to speculate that altered tumor vascularity may be implicated in the observed effect of ADAM12 on response to radiotherapy in rectal cancer. We conclude that ADAM12 represents a promising prognostic factor for stratification of rectal cancer patients receiving radiotherapy and suggest that targeting ADAM12 in combination with radiotherapy could potentially improve the treatment response.
AB - Radiotherapy is one of the most common cancer treatments, yet, some patients require high doses to respond. Therefore, the development of new strategies leans toward personalizing therapy to avoid unnecessary burden on cancer patients. This approach prevents the administration of ineffective treatments or uses combination strategies to increase the sensitivity of cancer cells. ADAM12 has been shown to be upregulated in many cancers and correlate with poor survival and chemoresistance, thus making it a potential candidate responsible for radioresistance. Here, we show that ADAM12 expression is upregulated in response to irradiation in both mouse and human cancer cells in vitro, as well as in tumor tissues from rectal cancer patients. Interestingly, the expression of ADAM12 following radiotherapy correlates with the initial disease stage and predicts the response of rectal cancer patients to the treatment. While we found no cell-autonomous effects of ADAM12 on the response of colon cancer cells to irradiation in vitro, depletion of ADAM12 expression markedly reduced the tumor growth of irradiated cancer cells when subcutaneously transplanted in syngeneic mice. Interestingly, loss of cancer cell-derived ADAM12 expression increased the number of CD31+FAP− cells in murine tumors. Moreover, conditioned medium from ADAM12−/− colon cancer cells led to increased tube formation when added to endothelial cell cultures. Thus, it is tempting to speculate that altered tumor vascularity may be implicated in the observed effect of ADAM12 on response to radiotherapy in rectal cancer. We conclude that ADAM12 represents a promising prognostic factor for stratification of rectal cancer patients receiving radiotherapy and suggest that targeting ADAM12 in combination with radiotherapy could potentially improve the treatment response.
U2 - 10.1038/s41417-023-00643-w
DO - 10.1038/s41417-023-00643-w
M3 - Journal article
C2 - 37495855
AN - SCOPUS:85165659040
VL - 30
SP - 1369
EP - 1381
JO - Cancer Gene Therapy
JF - Cancer Gene Therapy
SN - 0929-1903
ER -
ID: 361080291