Cardiac Remodeling in the Absence of Cardiac Contractile Dysfunction Is Sufficient to Promote Cancer Progression

Cardiovascular diseases and cancer are the leading cause of death worldwide. The two diseases share high co-prevalence and affect each other’s outcomes. Recent studies suggest that heart failure promotes cancer progression, although the question of whether cardiac remodeling in the absence of cardia...

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Main Authors: Lama Awwad, Tomer Goldenberg, Irina Langier-Goncalves, Ami Aronheim
Format: Article
Language:English
Published: MDPI AG 2022-03-01
Series:Cells
Subjects:
Online Access:https://www.mdpi.com/2073-4409/11/7/1108
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author Lama Awwad
Tomer Goldenberg
Irina Langier-Goncalves
Ami Aronheim
author_facet Lama Awwad
Tomer Goldenberg
Irina Langier-Goncalves
Ami Aronheim
author_sort Lama Awwad
collection DOAJ
description Cardiovascular diseases and cancer are the leading cause of death worldwide. The two diseases share high co-prevalence and affect each other’s outcomes. Recent studies suggest that heart failure promotes cancer progression, although the question of whether cardiac remodeling in the absence of cardiac contractile dysfunction promotes cancer progression remains unanswered. Here, we aimed to examine whether mild cardiac remodeling can promote tumor growth. We used low-phenylephrine (PE)-dose-infused in mice, together with breast cancer cells (polyoma middle T, PyMT), implanted in the mammary fat pad. Although cardiac remodeling, hypertrophy and fibrosis gene hallmarks were identified, echocardiography indicated no apparent loss of cardiac function. Nevertheless, in PE-infused mouse models, PyMT-cell-derived tumors grew larger and displayed increased cell proliferation. Consistently, serum derived from PE-infused mice resulted in increased cancer cell proliferation in vitro. ELISA and gene expression analysis identified periostin, fibronectin and CTGF as cardiac- and tumor-secreted factors that are highly abundant in PE-infused mice serum as compared with non-infused mice. Collectively, a low dose of PE infusion without the deterioration of cardiac function is sufficient to promote cancer progression. Hence, early detection and treatment of hypertension in healthy and cancer patients would be beneficial for improved outcomes.
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spelling doaj.art-b9f5031678a446d6a1e6a1a8d331c18d2023-11-30T23:03:36ZengMDPI AGCells2073-44092022-03-01117110810.3390/cells11071108Cardiac Remodeling in the Absence of Cardiac Contractile Dysfunction Is Sufficient to Promote Cancer ProgressionLama Awwad0Tomer Goldenberg1Irina Langier-Goncalves2Ami Aronheim3Department of Cell Biology and Cancer Science, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa 31096, IsraelDepartment of Cell Biology and Cancer Science, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa 31096, IsraelDepartment of Cell Biology and Cancer Science, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa 31096, IsraelDepartment of Cell Biology and Cancer Science, The Ruth and Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa 31096, IsraelCardiovascular diseases and cancer are the leading cause of death worldwide. The two diseases share high co-prevalence and affect each other’s outcomes. Recent studies suggest that heart failure promotes cancer progression, although the question of whether cardiac remodeling in the absence of cardiac contractile dysfunction promotes cancer progression remains unanswered. Here, we aimed to examine whether mild cardiac remodeling can promote tumor growth. We used low-phenylephrine (PE)-dose-infused in mice, together with breast cancer cells (polyoma middle T, PyMT), implanted in the mammary fat pad. Although cardiac remodeling, hypertrophy and fibrosis gene hallmarks were identified, echocardiography indicated no apparent loss of cardiac function. Nevertheless, in PE-infused mouse models, PyMT-cell-derived tumors grew larger and displayed increased cell proliferation. Consistently, serum derived from PE-infused mice resulted in increased cancer cell proliferation in vitro. ELISA and gene expression analysis identified periostin, fibronectin and CTGF as cardiac- and tumor-secreted factors that are highly abundant in PE-infused mice serum as compared with non-infused mice. Collectively, a low dose of PE infusion without the deterioration of cardiac function is sufficient to promote cancer progression. Hence, early detection and treatment of hypertension in healthy and cancer patients would be beneficial for improved outcomes.https://www.mdpi.com/2073-4409/11/7/1108cardiac remodelingcancer progressionsecreted factors
spellingShingle Lama Awwad
Tomer Goldenberg
Irina Langier-Goncalves
Ami Aronheim
Cardiac Remodeling in the Absence of Cardiac Contractile Dysfunction Is Sufficient to Promote Cancer Progression
Cells
cardiac remodeling
cancer progression
secreted factors
title Cardiac Remodeling in the Absence of Cardiac Contractile Dysfunction Is Sufficient to Promote Cancer Progression
title_full Cardiac Remodeling in the Absence of Cardiac Contractile Dysfunction Is Sufficient to Promote Cancer Progression
title_fullStr Cardiac Remodeling in the Absence of Cardiac Contractile Dysfunction Is Sufficient to Promote Cancer Progression
title_full_unstemmed Cardiac Remodeling in the Absence of Cardiac Contractile Dysfunction Is Sufficient to Promote Cancer Progression
title_short Cardiac Remodeling in the Absence of Cardiac Contractile Dysfunction Is Sufficient to Promote Cancer Progression
title_sort cardiac remodeling in the absence of cardiac contractile dysfunction is sufficient to promote cancer progression
topic cardiac remodeling
cancer progression
secreted factors
url https://www.mdpi.com/2073-4409/11/7/1108
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AT irinalangiergoncalves cardiacremodelingintheabsenceofcardiaccontractiledysfunctionissufficienttopromotecancerprogression
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