Maintenance of differentiation in primary cultures of avian tendon cells

Schwarz, Richard I.; Colarusso, Lucia; Doty, Paul

doi:10.1016/0014-4827(76)90299-8

Cited by 76 publications

(53 citation statements)

References 17 publications

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“…Moreover, this stiffening-induced accumulation was dominant or comparable with that due to serum (R serum ) up to 0.5% FBS (Fig. 2C inset and Table 1), which falls within the physiologic serum concentration for fibroblasts as reported elsewhere (29). To rule out that the large stiffening-induced accumulation in SFM was not due to the presence of insulin, cell density was measured in SFM not supplemented with ITS.…”

Section: Matrix Stiffening Alone Is Sufficient To Increase the Densitsupporting

confidence: 82%

Matrix Stiffening and β1 Integrin Drive Subtype-Specific Fibroblast Accumulation in Lung Cancer

Puig

Lugo

Gabasa

et al. 2015

Molecular Cancer Research

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The crucial role of tumor-associated fibroblasts (TAF) in cancer progression is now clear in non-small cell lung cancer (NSCLC). However, therapies against TAFs are limited due to a lack of understanding in the subtype-specific mechanisms underlying their accumulation. Here, the mechanical (i.e., matrix rigidity) and soluble mitogenic cues that drive the accumulation of TAFs from major NSCLC subtypes: adenocarcinoma (ADC) and squamous cell carcinoma (SCC) were dissected. Fibroblasts were cultured on substrata engineered to exhibit normal-or tumor-like stiffnesses at different serum concentrations, and critical regulatory processes were elucidated. In control fibroblasts from nonmalignant tissue, matrix stiffening alone increased fibroblast accumulation, and this mechanical effect was dominant or comparable with that of soluble growth factors up to 0.5% serum. The stimulatory cues of matrix rigidity were driven by b1 integrin mechanosensing through FAK (pY397), and were associated with a posttranscriptionally driven rise in b1 integrin expression. The latter mechano-regulatory circuit was also observed in TAFs but in a subtype-specific fashion, because SCC-TAFs exhibited higher FAK (pY397), b1 expression, and ERK1/2 (pT202/Y204) than ADCTAFs. Moreover, matrix stiffening induced a larger TAF accumulation in SCC-TAFs (>50%) compared with ADC-TAFs (10%-20%). In contrast, SCC-TAFs were largely serum desensitized, whereas ADC-TAFs responded to high serum concentration only. These findings provide the first evidence of subtype-specific regulation of NSCLC-TAF accumulation. Furthermore, these data support that therapies aiming to restore normal lung elasticity and/or b1 integrin-dependent mechano regulation may be effective against SCC-TAFs, whereas inhibiting stromal growth factor signaling may be effective against ADC-TAFs.Implications: This study reveals distinct mechanisms underlying the abnormal accumulation of tumor-supporting fibroblasts in two major subtypes of lung cancer, which will assist the development of personalized therapies against these cells.

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Section: Matrix Stiffening Alone Is Sufficient To Increase the Densitsupporting

confidence: 82%

Matrix Stiffening and β1 Integrin Drive Subtype-Specific Fibroblast Accumulation in Lung Cancer

Puig

Lugo

Gabasa

et al. 2015

Molecular Cancer Research

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“…Primary avian tendon (PAT) cells were prepared as described (14,15). Chicken embryo fibroblasts (CEF) were prepared as described (16).…”

Section: Methodsmentioning

confidence: 99%

“…Chicken embryo fibroblasts (CEF) were prepared as described (16). The wild type (wt) and the ts mutant of Prague A-RSV (LA24) were focus purified (17) (14,15).…”

Section: Methodsmentioning

confidence: 99%

Is the product of the src gene a promoter?

Bissell¹,

Hatié²,

Calvin³

1979

Proc. Natl. Acad. Sci. U.S.A.

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Addition of a potent promotor, 12-O-tetradecanoylphorbol 13-acetate (TPA), to primary avian tendon or chicken embryo fibroblast cells infected with a temperaturesensitive mutant of Rous sarcoma virus produced a complete transformed phenocopy at the non rmissive temperature by the criteria tested. While normal, uninfected cultures also shifted towards a transformed phenotype after TPA addition, they did not achieve the same degree of morphological and biochemical alteration seen in virus-infected, TPAtreated cells.It is proposed that viral carcinogenesis, despite its rapidity, may occur in two stages: an "initiation" step caused by expression of a part of viral genome other than src (or by integration) and a promotion step (itself a multistep process) caused by the activation of the src gene. The src gene product could be enhanced or replaced by other promoting agents.We have gained tremendous knowledge of the structure and the genetics of RNA tumor viruses in recent years (1-3), yet we know relatively little about the mechanism(s) of viral carcinogenesis. The early optimism that viral transformation could provide a simple model for studying malignancy and that, once we identified the "oncogene" (4), we would understand cancer, has given way to skepticism and to an abrupt shift of interest from tumor viruses to other environmental carcinogens.The rapidity and completeness by which RNA tumor viruses could transform cells in culture andthe simplicity of the assay systems were the initial arguments for the use of RNA tumor virus-transformed cells as models for studying malignancy. These same reasonings, however, now are used to The isolation of active ingredients of croton oil by Hecker (7) has opened a whole new area of research, that of mechanism of action of tumor-promoting agents 8-11. It is now apparent that many characteristics induced by Rous sarcoma viruses (RSVs) are also induced by tumor promoters (10, 11). The overlap, however, is incomplete. Indeed, most of the effects of tumor promoters on normal cultured cells are analogousqualitatively and quantitatively-to the effects of serum (12) or other growth factors and are less pronounced than those caused by viral transformation. In addition, some characteristics, such as transformed morphology (11) and growth in agar, are not induced by the promoters.In this paper we show that at 410C addition of 12-0-tetradecanoylphorbol 13-acetate (TPA), a potent chemical promoter, to chicken cells infected with LA24, a temperature-sensitive (ts) mutant of RSV with a defect in the sarc gene, produces a more exact phenocopy of transformed cells than does TPA treatment of normal cells. The product of the arc gene at the nonpermissive temperature, therefore, appears to be either activated or replaced by the promoter. We propose that the product of the src gene itself may be a promoter rather than the initiator of transformation and that viral carcinogenesis may occur in two stages similar to those operating in mouse skin (13). The predictions of the model and the a...

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“…Because eccentric muscle contractions were found to increase collagen breakdown in the patellar tendons, 4 increases in anaerobic metabolism (when tendons are becoming compliant through exercise) may be related to maintaining a low metabolic rate without the risk of ischemia and necrosis 9 and favoring collagen synthesis. 30 However, this anaerobic metabolism may also lead to slow recovery (or healing) following activity. 32 Because our subjects were healthy, this is likely a normal reversible response to the exercise; we do not know whether these findings would lead to a tendinopathic tendon.…”

mentioning

confidence: 99%

Increased Patellar Tendon Microcirculation and Reduction of Tendon Stiffness Following Knee Extension Eccentric Exercises

Yin

Chen

Wu³

et al. 2014

J Orthop Sports Phys Ther

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Tendons are fibrous connective tissues that are capable of transmitting mechanical loading and utilize elastic energy during locomotion. 29 Tendon adaptations to mechanical loads include changes in mechanical properties and metaboliccirculatory function. 11,13 Tendon mechanical properties determine stress and strain distribution within the tendon. 37,38,40 Tendon microcirculation reflects intratendinous metabolic demands and includes the distribution of blood flow and oxygen consumption in the arteriolar, capillary, and venular segments. 22,31Local blood flow is controlled by autoregulation (myogenic responses and metabolism) and shearing stress stimulation of the endothelium and neurohormones, 31 and is partially influenced by vessel radius and length (Poiseuille's equation). 5Viscoelastic behaviors of the vessels and tendons suggest that adaptation of tendon microcirculation during exercises may vary due to differences in tendons' plastic mechanical properties. 18,19,36 However, this theory has not been validated.Exercises involving movements that an individual is not used to and that reduce tendon stiffness, 26 as well as exercises that cause ischemia reperfusion, 1,21 are proposed as likely etiological factors in acute tendinopathies occurring when someone suddenly increases his or her level of physical activities ("weekend warrior" syndrome) or has eccentric exercise T T STUDY DESIGN: Controlled laboratory study. T T OBJECTIVES:To measure and compare patellar tendon stiffness and microcirculation in college tennis players and nonathletic students when performing eccentric knee extension exercises that do and do not reduce tendon stiffness. T T BACKGROUND:Previous studies suggest that tendon microcirculation response during exercises may vary based on the tendon's plastic properties. T T METHODS:The study included 3 groups of college-age male students: tennis players who performed 4 sets of either 40 (n = 12) or 80 (n = 13) repetitions of eccentric knee extension exercise and nonathletic students (n = 14) who performed 4 sets of 40 repetitions. Tendon stiffness was measured before and after exercise completion. Changes in total hemoglobin and oxygen saturation (OSat) were analyzed while performing the 4 sets. Comparisons were made within and between the groups. The level of association between tendon microcirculation and stiffness reduction was assessed. T T RESULTS:The 2 groups (player/4 × 80 and student/4 × 40) exhibiting patellar tendon stiffness reductions (P<.008) showed higher total hemoglobin and OSat levels, above the pre-exercise levels, in the fourth set compared to the first set of exercises (P<.004). The tennis players who performed 4 sets of 40 repetitions exhibited higher OSat levels in the fourth set than in the first set (P = .004) but had no reduction in tendon stiffness. Changes in OSat levels in the fourth set were correlated with patellar tendon stiffness reductions (r = -0.381, P = .02). T T CONCLUSION:We conclude that there was increased patellar tendon microcirculation after performing...

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Maintenance of differentiation in primary cultures of avian tendon cells

Cited by 76 publications

References 17 publications

Matrix Stiffening and β1 Integrin Drive Subtype-Specific Fibroblast Accumulation in Lung Cancer

Matrix Stiffening and β1 Integrin Drive Subtype-Specific Fibroblast Accumulation in Lung Cancer

Is the product of the src gene a promoter?

Increased Patellar Tendon Microcirculation and Reduction of Tendon Stiffness Following Knee Extension Eccentric Exercises

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