Chemotherapy treatment induces pro-invasive changes in liver ECM composition

Guarin, Justinne R.; Fatherree, Jackson P.; Oudin, Madeleine J.

doi:10.1016/j.matbio.2022.08.002

Cited by 16 publications

(8 citation statements)

References 46 publications

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“…Inhibition of integrin α 1 β 1 reduced tumor cell invasion in the ECM in chemotherapy-treated mice. Treatment with obtustatin, a KTS disintegrin, a specific inhibitor of α 1 β 1 , reduced the movement of triple-negative breast cancer cells inoculated on a V-type collagen matrix [ 20 ] and reduced the migration and invasion of neuroblastoma cells with high TRPM2 expression [ 21 ], indicating the potential of α 1 β 1 to increase cancer cell metastasis. These findings suggest that integrin α 1 β 1 is an important target for intervention in cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

Integrin Targeting Enhances the Antimelanoma Effect of Annexin V in Mice

Zhu

Gao

et al. 2023

IJMS

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Malignant melanoma, an increasingly common form of skin cancer, is a major threat to public health, especially when the disease progresses past skin lesions to the stage of advanced metastasis. Targeted drug development is an effective strategy for the treatment of malignant melanoma. In this work, a new antimelanoma tumor peptide, the lebestatin–annexin V (designated LbtA5) fusion protein, was developed and synthesized by recombinant DNA techniques. As a control, annexin V (designated ANV) was also synthesized by the same method. The fusion protein combines annexin V, which specifically recognizes and binds phosphatidylserine, with the disintegrin lebestatin (lbt), a polypeptide that specifically recognizes and binds integrin α1β1. LbtA5 was successfully prepared with good stability and high purity while retaining the dual biological activity of ANV and lbt. MTT assays demonstrated that both ANV and LbtA5 could reduce the viability of melanoma B16F10 cells, but the activity of the fusion protein LbtA5 was superior to that of ANV. The tumor volume growth was slowed in a mouse xenograft model treated with ANV and LbtA5, and the inhibitory effect of high concentrations of LbtA5 was significantly better than that of the same dose of ANV and was comparable to that of DTIC, a drug used clinically for melanoma treatment. The hematoxylin and eosin (H&E) staining test showed that ANV and LbtA5 had antitumor effects, but LbtA5 showed a stronger ability to induce melanoma necrosis in mice. Immunohistochemical experiments further showed that ANV and LbtA5 may inhibit tumor growth by inhibiting angiogenesis in tumor tissue. Fluorescence labeling experiments showed that the fusion of ANV with lbt enhanced the targeting of LbtA5 to mouse melanoma tumor tissue, and the amount of target protein in tumor tissue was significantly increased. In conclusion, effective coupling of the integrin α1β1-specific recognition molecule lbt confers stronger biological antimelanoma effects of ANV, which may be achieved by the dual effects of effective inhibition of B16F10 melanoma cell viability and inhibition of tumor tissue angiogenesis. The present study describes a new potential strategy for the application of the promising recombinant fusion protein LbtA5 in the treatment of various cancers, including malignant melanoma.

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Section: Discussionmentioning

confidence: 99%

Integrin Targeting Enhances the Antimelanoma Effect of Annexin V in Mice

Zhu

Gao

et al. 2023

IJMS

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“…Collagens, the most abundant component of the tumor ECM, were reported to regulate the breast cancer initiation and metastasis, including collagen I, 49 collagen VI, 50 and collagen XII 51 . Chemotherapy was further demonstrated to induce metastasis via its effects on ECM composition, which might contribute to the recurrence of breast cancer 10,52 . Fatherree et al 10 reported chemotherapy‐induced collagen IV abundant in tumor ECM and promoted invasion via activation of Src and focal adhesion kinase, while Guarin et al 52 found chemotherapy‐induced collagen V abundant in liver ECM and increased cancer cell invasion via α1β1 integrin and MAPK signaling.…”

Section: Discussionmentioning

confidence: 99%

“… 51 Chemotherapy was further demonstrated to induce metastasis via its effects on ECM composition, which might contribute to the recurrence of breast cancer. 10 , 52 Fatherree et al 10 reported chemotherapy‐induced collagen IV abundant in tumor ECM and promoted invasion via activation of Src and focal adhesion kinase, while Guarin et al 52 found chemotherapy‐induced collagen V abundant in liver ECM and increased cancer cell invasion via α1β1 integrin and MAPK signaling. Besides the direct composition investigations, Kay et al reported metabolic reprogramming was also involved in halting the production of a pro‐tumorigenic ECM by targeting collagen synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…10,52 Fatherree et al10 reported chemotherapy-induced collagen IV abundant in tumor ECM and promoted invasion via activation of Src and focal adhesion kinase, while Guarin et al52 found chemotherapy-induced collagen V abundant in liver ECM and increased cancer cell invasion via α1β1 integrin and MAPK signaling. Besides the direct composition investigations, Kay…”

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confidence: 99%

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Distinguished biomimetic dECM system facilitates early detection of metastatic breast cancer cells

Weng,

Li,

Zhu

et al. 2023

Bioengineering & Transla Med

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Breast cancer is the most prevalent malignant tumor affecting women's health. Bone is the most common distant metastatic organ, worsening the quality of life and increasing the mortality of patients. Early detection of breast cancer bone metastasis is urgent for halting disease progression and improving tumor prognosis. Recently, extracellular matrix (ECM) with biomimetic tissue niches opened a new avenue for tumor models in vitro. Here, we developed a biomimetic decellularized ECM (dECM) system to recapitulate bone niches at different situations, bone mimetic dECM from osteoblasts (BM‐ECM) and bone tumor mimetic dECM from osteosarcoma cells (OS‐ECM). The two kinds of dECMs exhibited distinct morphology, protein composition, and distribution. Interestingly, highly metastatic breast cancer cells tended to adhere and migrate on BM‐ECM, while lowly metastatic breast cancer cells preferred the OS‐ECM niche. Epithelial‐to‐mesenchymal transition was a potential mechanism to initiate the breast cancer cell migration on different biomimetic dECMs. Importantly, in the nude mice model, the dECM system captured metastatic breast cancer cells as early as 10 days after orthotopic transplantation in mammary gland pads, with higher signal on BM‐ECM than that on OS‐ECM. Collectively, the biomimetic dECM system might be a promising tumor model to distinguish the metastatic ability of breast cancer cells in vitro and to facilitate early detection of metastatic breast cancer cells in vivo, contributing to the diagnosis of breast cancer bone metastasis.

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“…Instead, metastasis is driven by multiple signaling pathways inside the cell in response to many different cues from the local tumor environment [ 12 , 13 ]. Recent studies have suggested that chemotherapy drugs commonly used to inhibit tumor growth do not target invading cells and may promote local invasion of the surviving cells in breast tumors [ 14 – 16 ]. Eradicating metastatic breast cancer requires an in-depth understanding of the mechanisms that drive tumor cell migration.…”

Section: Introductionmentioning

confidence: 99%

Cell morphology best predicts tumorigenicity and metastasis in vivo across multiple TNBC cell lines of different metastatic potential

Conner,

Guarin,

et al. 2024

Breast Cancer Res

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Background Metastasis is the leading cause of death in breast cancer patients. For metastasis to occur, tumor cells must invade locally, intravasate, and colonize distant tissues and organs, all steps that require tumor cell migration. The majority of studies on invasion and metastasis rely on human breast cancer cell lines. While it is known that these cells have different properties and abilities for growth and metastasis, the in vitro morphological, proliferative, migratory, and invasive behavior of these cell lines and their correlation to in vivo behavior is poorly understood. Thus, we sought to classify each cell line as poorly or highly metastatic by characterizing tumor growth and metastasis in a murine model of six commonly used human triple-negative breast cancer xenografts, as well as determine which in vitro assays commonly used to study cell motility best predict in vivo metastasis. Methods We evaluated the liver and lung metastasis of human TNBC cell lines MDA-MB-231, MDA-MB-468, BT549, Hs578T, BT20, and SUM159 in immunocompromised mice. We characterized each cell line's cell morphology, proliferation, and motility in 2D and 3D to determine the variation in these parameters between cell lines. Results We identified MDA-MB-231, MDA-MB-468, and BT549 cells as highly tumorigenic and metastatic, Hs578T as poorly tumorigenic and metastatic, BT20 as intermediate tumorigenic with poor metastasis to the lungs but highly metastatic to the livers, and SUM159 as intermediate tumorigenic but poorly metastatic to the lungs and livers. We showed that metrics that characterize cell morphology are the most predictive of tumor growth and metastatic potential to the lungs and liver. Further, we found that no single in vitro motility assay in 2D or 3D significantly correlated with metastasis in vivo. Conclusions Our results provide an important resource for the TNBC research community, identifying the metastatic potential of 6 commonly used cell lines. Our findings also support the use of cell morphological analysis to investigate the metastatic potential and emphasize the need for multiple in vitro motility metrics using multiple cell lines to represent the heterogeneity of metastasis in vivo.

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Chemotherapy treatment induces pro-invasive changes in liver ECM composition

Cited by 16 publications

References 46 publications

Integrin Targeting Enhances the Antimelanoma Effect of Annexin V in Mice

Integrin Targeting Enhances the Antimelanoma Effect of Annexin V in Mice

Distinguished biomimetic dECM system facilitates early detection of metastatic breast cancer cells

Cell morphology best predicts tumorigenicity and metastasis in vivo across multiple TNBC cell lines of different metastatic potential

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