Research
Invasion II: Signaling Cooperation
As tumor progression continues, signalling cooperation and heterogeneity drive muscle invasion of a specific phenotype in our mouse xenograft model. Tumor invasion of wild-type DU145 [WT] (A), and a mutant DU145 in which the α6 integrin cannot be clipped [AA] (B), and WT:AA (C) in a xenograft model by auto-fluorescence imaging of H&E (D is a section of A) tissue sections of mouse diaphragm. The depth of invasion (F), number of invading cells for each cell type, WT, AA, and A6KO (G), and number of cell types in a 1:1 mixture of WT and AA cells (H) was quantified using the entire diaphragm from three mice for each condition. (E) AA cells within the 1:1 WT:AA mixture breached the muscle barrier (white line) as detected by RFP-H2B reporter (brown nuclei).
Tumor clusters exhibit functional diversity, aiding invasion and migration into oxygenated muscle. Our model tested the need for different biophysical traits within the unit and uncovered specific coordinated roles. Mixed biophysical phenotypes of tumor cells within a population can provide functional advantages for tumor invasion into and through muscle that can be potentially inhibited by a synthetic cell adhesion molecule.
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Marr KD, Gard JMC, Harryman WL, Keeswood EJ, Paxson AI, Wolgemuth C, Knudsen BS, Nagle RB, Hazlehurst L, Sorbellini M, Cress AE. Biophysical phenotype mixtures reveal advantages for tumor muscle invasion in vivo. Biophys J. 2023 Nov 7;122(21):4194-4206. doi: 10.1016/j.bpj.2023.09.016. Epub 2023 Sep 26. PMID: 37766428; PMCID: PMC10645557.
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Jensen CC, Clements AN, Liou H, Ball LE, Bethard JR, Langlais PR, Toth RK, Chauhan SS, Casillas AL, Daulat SR, Kraft AS, Cress AE, Miranti CK, Mouneimne G, Rogers GC, Warfel NA. PIM1 phosphorylates ABI2 to enhance actin dynamics and promote tumor invasion. J Cell Biol. 2023 Jun 5;222(6):e202208136. doi: 10.1083/jcb.202208136. Epub 2023 Apr 12. PMID: 37042842; PMCID: PMC10103708.
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Pollan SG, Teng PC, Jan YJ, Livingstone J, Huang C, Kim M, Mariscal J, Rodriguez M, Chen JF, You S, DiVizio D, Boutros PC, Chan KS, Rasorenova O, Cress AE, Spassov D, Moasser M, Posadas EM, Freedland SJ, Freeman MR, Zheng JJ, Knudsen BS. Loss of CDCP1 triggers FAK activation in detached prostate cancer cells. Am J Clin Exp Urol. 2021 Aug 25;9(4):350-366. PMID: 34541033; PMCID: PMC8446766.
